Role of uPA and uPAR in Human Glioma Invasiveness

Summary

Principal Investigator: JASTI RAO
Abstract: DESCRIPTION (provided by applicant): Malignant brain tumors represent one of the most refractory cancers to therapy and remain incurable. Gliomas represent the most common type of brain tumors that occur in various grades, with the patient's prognosis inversely proportional to the grade. The long-term objective of my laboratory is to understand the cellular and molecular mechanisms that underlie tumor invasiveness in human gliomas. My laboratory has been active in the study of proteases and the biology of brain tumors, and data generated so far have indicated that changes in proteases are correlated with the changes in the grade of the tumors. The hypotheses is: Regulation of uPAR and uPA expression in human gliomas via a plasmid/Ad construct expressing siRNA for and uPAR and uPA message will inhibit tumor growth, invasion and angiogenesis. The Specific Aims to address these hypothesis are as follows: Specific Aim 1. Evaluate the effect of vectors expressing siRNA targeting uPAR and uPA (pU2/AdU2) on glioma cell growth, attachment, migration and invasion in vitro, la. Determine the effect of vectors expressing siRNA against uPAR and uPA single or bicistronic constructs (puPAR, puPA and pU2) on uPAR and uPA levels in glioblastoma cell lines. Ib. Compare the effect of the single or bicistronic siRNA constructs (puPAR, puPA and pU2) on glioma growth, adhesion, apoptosis and migration with that of control/mock EV (empty vector) and SV (scrambled vector) in vitro. Ic. Investigate the effect of the single or bicistronic siRNA constructs (puPAR, puPA and pU2) on the invasive behavior of human glioblastoma cells in in vitro models with that of control/mock, EV (empty vector) and SV (scrambled vector). Specific Aim 2. Determine the in vivo effects of single or bicistronic siRNA constructs for uPAR and uPA (puPAR, puPA and pU2 or Ad-uPAR/Ad-uPA/AduPAR- uPA) on invasion, angiogenesis and tumorigenicity in nude mice. 2a. Access the ability of the puPA/puPAR/pU2 constructs in pre-established intracranial tumor growth or invasiveness of human glioblastoma cell lines (SNB19 and U251) injected intracerebrally in nude mice. 2b. Determine the effect of puPA/puPAR/pU2/AdU2 constructs in preestablished intracranial tumor growth or invasiveness of two xenografts and U87 sense SPARC stable cells (U87SS) in nude mice. 2c. Evaluate the effect of single or bicistronic siRNA constructs for uPAR and uPA (puPAR, puPA and pU2/AdU2) on cerebral angiogenesis in both in vitro and in vivo models. We anticipate that these results will substantially augment our understanding of how uPAR and uPA molecules are regulated;thus, information gained should be of help in developing new therapeutic approaches to treat glioblastomas.
Funding Period: 1998-05-05 - 2010-04-30
more information: NIH RePORT

Top Publications

  1. pmc uPA and uPAR shRNA inhibit angiogenesis via enhanced secretion of SVEGFR1 independent of GM-CSF but dependent on TIMP-1 in endothelial and glioblastoma cells
    Hari Raghu
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, USA
    Mol Oncol 6:33-47. 2012
  2. pmc Small interfering RNA-directed knockdown of uracil DNA glycosylase induces apoptosis and sensitizes human prostate cancer cells to genotoxic stress
    Sai Murali Krishna Pulukuri
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, USA
    Mol Cancer Res 7:1285-93. 2009
  3. pmc Therapeutic potential of siRNA-mediated targeting of urokinase plasminogen activator, its receptor, and matrix metalloproteinases
    Christopher S Gondi
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA
    Methods Mol Biol 487:267-81. 2009
  4. pmc MMP-2 alters VEGF expression via alphaVbeta3 integrin-mediated PI3K/AKT signaling in A549 lung cancer cells
    Chandramu Chetty
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    Int J Cancer 127:1081-95. 2010
  5. pmc Targeting MMP-9, uPAR, and cathepsin B inhibits invasion, migration and activates apoptosis in prostate cancer cells
    A K Nalla
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, USA
    Cancer Gene Ther 17:599-613. 2010
  6. pmc Epigenetic upregulation of urokinase plasminogen activator promotes the tropism of mesenchymal stem cells for tumor cells
    Sai Murali Krishna Pulukuri
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, USA
    Mol Cancer Res 8:1074-83. 2010
  7. pmc Suppression of uPA and uPAR attenuates angiogenin mediated angiogenesis in endothelial and glioblastoma cell lines
    Hari Raghu
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, United States of America
    PLoS ONE 5:e12458. 2010
  8. pmc Downregulation of uPAR and cathepsin B induces apoptosis via regulation of Bcl-2 and Bax and inhibition of the PI3K/Akt pathway in gliomas
    Ramarao Malla
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, United States of America
    PLoS ONE 5:e13731. 2010
  9. pmc Specific knockdown of uPA/uPAR attenuates invasion in glioblastoma cells and xenografts by inhibition of cleavage and trafficking of Notch -1 receptor
    Hari Raghu
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, One Illini Drive, Peoria, IL 61605, USA
    Mol Cancer 10:130. 2011
  10. pmc Inhibition of matrix metalloproteinase-2 enhances radiosensitivity by abrogating radiation-induced FoxM1-mediated G2/M arrest in A549 lung cancer cells
    Chandramu Chetty
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA
    Int J Cancer 124:2468-77. 2009

Scientific Experts

  • Athanassios P Kyritsis
  • Hari Raghu
  • Jasti S Rao
  • Christopher S Gondi
  • Meena Gujrati
  • Dzung H Dinh
  • Sajani S Lakka
  • Sai Murali Krishna Pulukuri
  • Chandramu Chetty
  • William C Olivero
  • Sateesh Kunigal
  • Venkata Ramesh Dasari
  • Shakuntala Kondraganti
  • Praveen Bhoopathi
  • J S Rao
  • Norman Estes
  • S M Pulukuri
  • Sreelatha Gopinath
  • Sravan K Vanamala
  • Jeffrey D Klopfenstein
  • Odysseas Kargiotis
  • Daniel G Spomar
  • Padmaja Tummalapalli
  • S S Lakka
  • C Chetty
  • Liang Li
  • Neelima Kandhukuri
  • Sai MuraliKrishna Pulukuri
  • A K Nalla
  • Ramarao Malla
  • B Gorantla
  • C S Gondi
  • Venkateswara Rao Gogineni
  • Bharathi Gorantla
  • O Kargiotis
  • Andrew J Tsung
  • Narasimharao Nalabothula
  • Joseph George
  • Ian McCutcheon
  • Ramesh Subramanian
  • Aman Jutla
  • Niranjan Yanamandra
  • Sanjeeva Mohanam
  • Kiranmai Alapati
  • Lavanya Talluri
  • J A Knost
  • Prasanna Kumar Sodadasu
  • James A Knost
  • Roger Geiss
  • Pushpa Joseph
  • A J Tsung
  • M Gujrati
  • Venkateswara Gogineni
  • D H Dinh
  • Daniel Spomar
  • N Estes
  • Christopher A Sloffer
  • Craig Cady
  • Kay L Saving
  • J Patel
  • Jitendra Patel
  • S Patibandla
  • P Bhoopathi
  • Velidi H Rao
  • Chrissa Sioka
  • Pushpa A Joseph
  • Subramanyam Chittivelu
  • Christopher Gondi

Detail Information

Publications59

  1. pmc uPA and uPAR shRNA inhibit angiogenesis via enhanced secretion of SVEGFR1 independent of GM-CSF but dependent on TIMP-1 in endothelial and glioblastoma cells
    Hari Raghu
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, USA
    Mol Oncol 6:33-47. 2012
    ..Taken together, these results suggest that the uPA/uPAR system could prove beneficial as an indirect target for inhibition of angiogenesis in glioblastoma...
  2. pmc Small interfering RNA-directed knockdown of uracil DNA glycosylase induces apoptosis and sensitizes human prostate cancer cells to genotoxic stress
    Sai Murali Krishna Pulukuri
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, USA
    Mol Cancer Res 7:1285-93. 2009
    ..Taken together, these findings indicate that RNA interference-directed targeting of UNG is a convenient, novel tool for studying the biological role of UNG and raises the potential of its application for prostate cancer therapy...
  3. pmc Therapeutic potential of siRNA-mediated targeting of urokinase plasminogen activator, its receptor, and matrix metalloproteinases
    Christopher S Gondi
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA
    Methods Mol Biol 487:267-81. 2009
    ..In this chapter we discuss the therapeutic potential of siRNA-mediated targeting of the uPAR-uPA system and MMPs as therapeutic agents for the treatment of cancer...
  4. pmc MMP-2 alters VEGF expression via alphaVbeta3 integrin-mediated PI3K/AKT signaling in A549 lung cancer cells
    Chandramu Chetty
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    Int J Cancer 127:1081-95. 2010
    ..In summary, these data provide new insights into the mechanisms underlying MMP-2-mediated VEGF expression in lung tumor angiogenesis...
  5. pmc Targeting MMP-9, uPAR, and cathepsin B inhibits invasion, migration and activates apoptosis in prostate cancer cells
    A K Nalla
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, USA
    Cancer Gene Ther 17:599-613. 2010
    ..In conclusion, we report that the siRNA-mediated knockdown of MMP-9, uPAR, and CB inhibits invasiveness and migration of prostate cancer cells and leads to apoptosis both in vitro and in vivo...
  6. pmc Epigenetic upregulation of urokinase plasminogen activator promotes the tropism of mesenchymal stem cells for tumor cells
    Sai Murali Krishna Pulukuri
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, USA
    Mol Cancer Res 8:1074-83. 2010
    ..These results have significant implications for the development of MSC-mediated, tumor-selective gene therapies...
  7. pmc Suppression of uPA and uPAR attenuates angiogenin mediated angiogenesis in endothelial and glioblastoma cell lines
    Hari Raghu
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, United States of America
    PLoS ONE 5:e12458. 2010
    ..The exact mechanism by which inhibition of angiogenesis takes place is not clearly understood...
  8. pmc Downregulation of uPAR and cathepsin B induces apoptosis via regulation of Bcl-2 and Bax and inhibition of the PI3K/Akt pathway in gliomas
    Ramarao Malla
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, United States of America
    PLoS ONE 5:e13731. 2010
    ..uPAR and cathepsin B are known to be overexpressed in high-grade gliomas and are strongly correlated with invasive cancer phenotypes...
  9. pmc Specific knockdown of uPA/uPAR attenuates invasion in glioblastoma cells and xenografts by inhibition of cleavage and trafficking of Notch -1 receptor
    Hari Raghu
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, One Illini Drive, Peoria, IL 61605, USA
    Mol Cancer 10:130. 2011
    ..Previous studies from our lab have also shown that uPA/uPAR down regulation inhibits cancer cell invasion in SNB 19 GBM cells...
  10. pmc Inhibition of matrix metalloproteinase-2 enhances radiosensitivity by abrogating radiation-induced FoxM1-mediated G2/M arrest in A549 lung cancer cells
    Chandramu Chetty
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA
    Int J Cancer 124:2468-77. 2009
    ....
  11. pmc RNAi-mediated downregulation of radiation-induced MMP-9 leads to apoptosis via activation of ERK and Akt in IOMM-Lee cells
    Venkateswara Rao Gogineni
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    Int J Oncol 34:209-18. 2009
    ....
  12. pmc uPA/uPAR downregulation inhibits radiation-induced migration, invasion and angiogenesis in IOMM-Lee meningioma cells and decreases tumor growth in vivo
    Odysseas Kargiotis
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    Int J Oncol 33:937-47. 2008
    ..Thus, the specific targeting of proteases via RNA interference could augment the therapeutic effect of radiation and prevent the adverse effects resulting from tumor cells that receive sublethal doses of radiation within the tumor mass...
  13. pmc Antiangiogenic therapy in brain tumors
    Sajani S Lakka
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, 1 Illini Drive, Peoria, IL 61605, USA
    Expert Rev Neurother 8:1457-73. 2008
    ....
  14. pmc Simultaneous downregulation of uPAR and MMP-9 induces overexpression of the FADD-associated protein RIP and activates caspase 9-mediated apoptosis in gliomas
    Christopher S Gondi
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    Int J Oncol 33:783-90. 2008
    ..Based on our results we conclude that the simultaneous downregulation of uPAR and MMP-9 induces apoptosome-mediated apoptosis...
  15. pmc Tissue inhibitor of metalloproteinase 3 suppresses tumor angiogenesis in matrix metalloproteinase 2-down-regulated lung cancer
    Chandramu Chetty
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA
    Cancer Res 68:4736-45. 2008
    ..These experiments provide the first evidence that inhibition of p-AKT and induction of p-ERK1/2 are crucial events in the induction of TIMP-3-mediated endothelial apoptosis in MMP-2 inhibited lung tumors...
  16. pmc Matrix metalloproteinase-9 inhibition down-regulates radiation-induced nuclear factor-kappa B activity leading to apoptosis in breast tumors
    Sateesh Kunigal
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA
    Clin Cancer Res 14:3617-26. 2008
    ..In the present study, we show that the modulation of MMP-9 expression, using adenoviral-mediated transfer of the antisense MMP-9 gene (MMP-9 adenoviral construct, Ad-MMP-9), affects breast cancer sensitivity to radiation...
  17. pmc Matrix metalloproteinase-1 promotes prostate tumor growth and metastasis
    Sai Murali Krishna Pulukuri
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, USA
    Int J Oncol 32:757-65. 2008
    ..Collectively, our findings suggest that MMP-1 plays an important role in prostate cancer progression during the invasive and metastatic stages of the disease...
  18. pmc Downregulation of matrix metalloproteinase-2 (MMP-2) utilizing adenovirus-mediated transfer of small interfering RNA (siRNA) in a novel spinal metastatic melanoma model
    Andrew J Tsung
    Department of Neurosurgery, University of Illinois College of Medicine, Peoria, IL 61605, USA
    Int J Oncol 32:557-64. 2008
    ..This novel experimental model revealed that adenoviral-mediated transfer of RNA interference against MMP-2 results in the retention of neurological function and significantly inhibited tumor growth...
  19. pmc Adenovirus-mediated transfer of siRNA against MMP-2 mRNA results in impaired invasion and tumor-induced angiogenesis, induces apoptosis in vitro and inhibits tumor growth in vivo in glioblastoma
    O Kargiotis
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    Oncogene 27:4830-40. 2008
    ..Thus, specific targeting of MMP-2 may provide a novel, efficient approach for the treatment of gliomas and improve the poor outcomes of patients with these brain tumors...
  20. pmc Stat3-siRNA induces Fas-mediated apoptosis in vitro and in vivo in breast cancer
    Sateesh Kunigal
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    Int J Oncol 34:1209-20. 2009
    ..Thus, targeting Stat3 signaling using siRNA may serve as a novel therapeutic strategy for the treatment of breast cancers expressing constitutively activated Stat3...
  21. pmc Inherited predisposition to glioma
    Athanassios P Kyritsis
    University Hospital of Ioannina, Neurosurgical Research Institute, University of Ioannina School of Medicine, University Campus, Ioannina 45110, Greece
    Neuro Oncol 12:104-13. 2010
    ..Future molecular diagnosis may identify new genomic regions that could harbor genes important for glioma predisposition and aid in the early diagnosis of these patients and genetic counseling of their families...
  22. pmc siRNA-mediated simultaneous downregulation of uPA and its receptor inhibits angiogenesis and invasiveness triggering apoptosis in breast cancer cells
    Ramesh Subramanian
    Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, USA
    Int J Oncol 28:831-9. 2006
    ....
  23. pmc Doxorubicin-mediated apoptosis in glioma cells requires NFAT3
    Sreelatha Gopinath
    Department of Cancer Biology and Pharmacology, College of Medicine at Peoria, University of Illinois, 1649 Peoria, IL 61656, USA
    Cell Mol Life Sci 66:3967-78. 2009
    ..Taken together, these results indicate that NFAT3 is a prerequisite for the induction of DOX-mediated apoptosis in glioma cells...
  24. pmc RNAi-mediated downregulation of MMP-2 activates the extrinsic apoptotic pathway in human glioma xenograft cells
    Christopher S Gondi
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    Int J Oncol 35:851-9. 2009
    ..In summary, it is evident from our results that MMP-2 downregulation induces caspase-8 and AIF-mediated apoptosis and, as such, shows potential for glioma therapy...
  25. ncbi Viruses, gene therapy and stem cells for the treatment of human glioma
    A P Kyritsis
    Department of Neurology, University Hospital of Ioannina, Ioannina 45110, Greece
    Cancer Gene Ther 16:741-52. 2009
    ..Nevertheless, continuing research in better vector development may overcome these limitations and offer a therapeutic advantage over the standard therapies for glioma...
  26. pmc MMP-2 downregulation mediates differential regulation of cell death via ErbB-2 in glioma xenografts
    Christopher S Gondi
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    Int J Oncol 35:257-63. 2009
    ..Our results suggest that MMP-2 may play a role in a hitherto unknown signaling pathway mediated via ErbB-2 in certain cancer cell types...
  27. pmc Effect of human umbilical cord blood cells on Ang-II-induced hypertrophy in mice
    Sravan K Vanamala
    Department of Cancer Biology and Pharmacology, University of Illinois, College of Medicine at Peoria, Peoria, IL 61656, USA
    Biochem Biophys Res Commun 386:386-91. 2009
    ..Our findings support hUCB as a feasible model for experimentation in stem cell therapy and emphasize the relevance of the hUCB in reversing heart failure conditions...
  28. pmc Frequent loss of cystatin E/M expression implicated in the progression of prostate cancer
    S M Pulukuri
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, 61605, USA
    Oncogene 28:2829-38. 2009
    ....
  29. pmc Concepts in in vivo siRNA delivery for cancer therapy
    Christopher S Gondi
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    J Cell Physiol 220:285-91. 2009
    ..This review presents the early and intriguing successes of using siRNAs for in vivo gene silencing and its use as a possible cancer therapeutics...
  30. pmc Blockade of tumor growth due to matrix metalloproteinase-9 inhibition is mediated by sequential activation of beta1-integrin, ERK, and NF-kappaB
    Praveen Bhoopathi
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA
    J Biol Chem 283:1545-52. 2008
    ..In addition, ERK activation plays an active role in this process and functions upstream of NF-kappaB activation to initiate the apoptotic signal...
  31. pmc Inhibition of histone deacetylase activity promotes invasion of human cancer cells through activation of urokinase plasminogen activator
    Sai Murali Krishna Pulukuri
    Department of Cancer Biology, University of Illinois College of Medicine, Peoria, Illinois 61656, USA
    J Biol Chem 282:35594-603. 2007
    ....
  32. pmc Sense p16 and antisense uPAR bicistronic construct inhibits angiogenesis and induces glioma cell death
    Narasimharao Nalabothula
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA
    Int J Oncol 30:669-78. 2007
    ....
  33. pmc RNA interference-mediated simultaneous down-regulation of urokinase-type plasminogen activator receptor and cathepsin B induces caspase-8-mediated apoptosis in SNB19 human glioma cells
    Christopher S Gondi
    Program of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA
    Mol Cancer Ther 5:3197-208. 2006
    ..Our study shows the potential of RNAi-mediated down-regulation of uPAR and cathepsin B in developing new therapeutics for gliomas...
  34. pmc SPARC-induced migration of glioblastoma cell lines via uPA-uPAR signaling and activation of small GTPase RhoA
    Sateesh Kunigal
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    Int J Oncol 29:1349-57. 2006
    ..Our results show that the small GTPase RhoA was a critical mediator of invasion or migration in the uPA-uPAR/PI3-K signaling pathway...
  35. pmc CpG island promoter methylation and silencing of 14-3-3sigma gene expression in LNCaP and Tramp-C1 prostate cancer cell lines is associated with methyl-CpG-binding protein MBD2
    S M Pulukuri
    Program of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria, IL 61656, USA
    Oncogene 25:4559-72. 2006
    ....
  36. pmc Restoration of tissue factor pathway inhibitor inhibits invasion and tumor growth in vitro and in vivo in a malignant meningioma cell line
    Shakuntala Kondraganti
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, 61656, USA
    Int J Oncol 29:25-32. 2006
    ..Finally, TFPI-2 overexpression inhibited intracranial tumor formation in nude mice. Our data substantiate our previous observation that TFPI-2 plays an important role in tumor progression and has potential in anti-cancer therapy...
  37. pmc RNAi-mediated downregulation of urokinase plasminogen activator and its receptor in human meningioma cells inhibits tumor invasion and growth
    Shakuntala Kondraganti
    Program of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria, IL 61656, USA
    Int J Oncol 28:1353-60. 2006
    ..These findings suggest that siRNA can be used as a potent and specific therapeutic tool for the treatment of malignant meningiomas in humans...
  38. pmc Down-regulation of uPAR and cathepsin B retards cofilin dephosphorylation
    Christopher S Gondi
    Program of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, USA
    Int J Oncol 28:633-9. 2006
    ..Our results demonstrate the relevance of uPAR in cytoskeletal dynamics and the potential of uPAR and cathepsin B as targets in the treatment of malignant gliomas...
  39. ncbi Proteases and glioma angiogenesis
    Sajani S Lakka
    Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine Peoria, Peoria, IL 61605, USA
    Brain Pathol 15:327-41. 2005
    ..However, careful testing of these combinations are most important because multiple effects of these combinations play a significant role in angiogenesis...
  40. pmc Inhibition of invasion, angiogenesis, tumor growth, and metastasis by adenovirus-mediated transfer of antisense uPAR and MMP-9 in non-small cell lung cancer cells
    Jasti S Rao
    Program of Cancer Biology, University of Illinois College of Medicine Peoria, 61605, USA
    Mol Cancer Ther 4:1399-408. 2005
    ..In summary, adenovirus-mediated inhibition of uPA-uPAR interaction and MMP-9 on the cell surface may be a promising anti-invasion and antimetastatic strategy for cancer gene therapy...
  41. pmc RNA interference-directed knockdown of urokinase plasminogen activator and urokinase plasminogen activator receptor inhibits prostate cancer cell invasion, survival, and tumorigenicity in vivo
    Sai MuraliKrishna Pulukuri
    Department of Biomedical and Therapeutic Sciences Program of Cancer Biology, University of Illinois College of Medicine, Peoria, Illinois 61656, USA
    J Biol Chem 280:36529-40. 2005
    ..Thus, RNA interference-directed targeting of uPA and uPAR is a convenient and novel tool for studying the biological role of the uPA-uPAR system and raises the potential of its application for prostate cancer therapy...
  42. ncbi Specific interference of urokinase-type plasminogen activator receptor and matrix metalloproteinase-9 gene expression induced by double-stranded RNA results in decreased invasion, tumor growth, and angiogenesis in gliomas
    Sajani S Lakka
    Departments of Biomedical and Therapeutic Sciences Program of Cancer Biology, College of Medicine, University of Illinois, Peoria, IL 61656, USA
    J Biol Chem 280:21882-92. 2005
    ..Our results provide evidence that the use of hairpin siRNA expression vectors for uPAR and MMP-9 may provide an effective tool for cancer therapy...
  43. ncbi Activation of p53/p21Waf1/Cip1 pathway by 5-aza-2'-deoxycytidine inhibits cell proliferation, induces pro-apoptotic genes and mitogen-activated protein kinases in human prostate cancer cells
    Sai Murali Krishna Pulukuri
    Program of Cancer Biology and Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine Peoria, Peoria, IL 61605, USA
    Int J Oncol 26:863-71. 2005
    ..Therefore, our data indicate that p53 status in tumor cells may be critical for the clinical efficacy and toxicity of 5-aza-CdR...
  44. pmc Demethylation-linked activation of urokinase plasminogen activator is involved in progression of prostate cancer
    Sai Murali Krishna Pulukuri
    Department of Cancer Biology and Pharmacology, College of Medicine, University of Illinois at Peoria, Peoria, IL 61656, USA
    Cancer Res 67:930-9. 2007
    ..Collectively, these findings strongly suggest that DNA demethylation is a common mechanism underlying the abnormal expression of uPA and is a critical contributing factor to the malignant progression of human prostate tumors...
  45. pmc Epigenetic inactivation of the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene in human prostate tumors
    S M Pulukuri
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, USA
    Oncogene 26:5229-37. 2007
    ..These results suggest that the downregulation of the TIMP-2 gene is associated with promoter methylation and that this may play an important role in prostate cancer progression during the invasive and metastatic stages of the disease...
  46. pmc Axonal remyelination by cord blood stem cells after spinal cord injury
    Venkata Ramesh Dasari
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois 61605, USA
    J Neurotrauma 24:391-410. 2007
    ..Therefore, hUCB facilitate functional recovery after moderate SCI and may prove to be a useful therapeutic strategy to repair the injured spinal cord...
  47. pmc RNAi-mediated abrogation of cathepsin B and MMP-9 gene expression in a malignant meningioma cell line leads to decreased tumor growth, invasion and angiogenesis
    Padmaja Tummalapalli
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA
    Int J Oncol 31:1039-50. 2007
    ..Furthermore, these observations demonstrate that the simultaneous RNAi-mediated targeting of cathepsin B and MMP-9 has potential application for the treatment of human meningiomas...
  48. pmc Umbilical cord blood stem cell mediated downregulation of fas improves functional recovery of rats after spinal cord injury
    Venkata Ramesh Dasari
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61656, USA
    Neurochem Res 33:134-49. 2008
    ..Taken together, our results indicate that hUCB-mediated downregulation of Fas and caspases leads to functional recovery of hind limbs of rats after SCI...
  49. pmc RNAi-mediated downregulation of urokinase plasminogen activator receptor and matrix metalloprotease-9 in human breast cancer cells results in decreased tumor invasion, angiogenesis and growth
    Sateesh Kunigal
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA
    Int J Cancer 121:2307-16. 2007
    ..In conclusion, our results provide evidence that the simultaneous downregulation of uPAR and MMP-9 using RNAi technology may provide an effective tool for breast cancer therapy...
  50. pmc Small interfering RNA directed reversal of urokinase plasminogen activator demethylation inhibits prostate tumor growth and metastasis
    Sai Murali Krishna Pulukuri
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA
    Cancer Res 67:6637-46. 2007
    ....
  51. pmc Intraperitoneal injection of a hairpin RNA-expressing plasmid targeting urokinase-type plasminogen activator (uPA) receptor and uPA retards angiogenesis and inhibits intracranial tumor growth in nude mice
    Christopher S Gondi
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois 61605, USA
    Clin Cancer Res 13:4051-60. 2007
    ..The purpose of this study was to evaluate the therapeutic potential of using plasmid-expressed RNA interference (RNAi) targeting urokinase-type plasminogen activator (uPA) receptor (uPAR) and uPA to treat human glioma...
  52. pmc MMP-2 siRNA induced Fas/CD95-mediated extrinsic II apoptotic pathway in the A549 lung adenocarcinoma cell line
    C Chetty
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, USA
    Oncogene 26:7675-83. 2007
    ..This is the first report, to our knowledge, showing that MMP-2 inhibition upregulates TIMP-3 levels, which in turn, promotes apoptosis in lung cancer...
  53. pmc Restoration of tissue factor pathway inhibitor-2 in a human glioblastoma cell line triggers caspase-mediated pathway and apoptosis
    Joseph George
    Department of Cancer Biology, University of Illinois, College of Medicine at Peoria, Peoria, Illinois, USA
    Clin Cancer Res 13:3507-17. 2007
    ..Tissue factor pathway inhibitor-2 (TFPI-2) is a protease inhibitor that is abundant in the extracellular matrix and highly expressed in noninvasive cells but absent or undetectable in highly invasive human glioblastoma cells...
  54. pmc Mesenchymal stem cells from rat bone marrow downregulate caspase-3-mediated apoptotic pathway after spinal cord injury in rats
    Venkata Ramesh Dasari
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61656, USA
    Neurochem Res 32:2080-93. 2007
    ..The ability of rMSC to incorporate into the spinal cord, differentiate and to improve locomotor recovery hold promise for a potential cure after SCI...
  55. pmc Down-regulation of uPAR and uPA activates caspase-mediated apoptosis and inhibits the PI3K/AKT pathway
    Christopher S Gondi
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    Int J Oncol 31:19-27. 2007
    ..Our studies provide evidence for the presence of a feedback response of the uPAR-uPA system indicative of the multifaceted role of uPAR, and also the therapeutic potential of simultaneously targeting uPAR and uPA in cancer patients...
  56. pmc RNA interference-mediated targeting of urokinase plasminogen activator receptor and matrix metalloproteinase-9 gene expression in the IOMM-lee malignant meningioma cell line inhibits tumor growth, tumor cell invasion and angiogenesis
    Padmaja Tummalapalli
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
    Int J Oncol 31:5-17. 2007
    ..In addition, the present study indicated that targeting both the proteins simultaneously augmented the therapeutic treatment of human meningiomas...
  57. pmc MMP-9 short interfering RNA induced senescence resulting in inhibition of medulloblastoma growth via p16(INK4a) and mitogen-activated protein kinase pathway
    Jasti S Rao
    Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois 61605, USA
    Cancer Res 67:4956-64. 2007
    ..These studies validate the usefulness of targeting MMP-9 and provide a novel perspective in the treatment of medulloblastoma...
  58. pmc Transfection with anti-p65 intrabody suppresses invasion and angiogenesis in glioma cells by blocking nuclear factor-kappaB transcriptional activity
    Liang Li
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois 61605, USA
    Clin Cancer Res 13:2178-90. 2007
    ....
  59. ncbi Recombinant adeno-associated virus (rAAV) expressing TFPI-2 inhibits invasion, angiogenesis and tumor growth in a human glioblastoma cell line
    Niranjan Yanamandra
    Program of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria, IL 61656, USA
    Int J Cancer 115:998-1005. 2005
    ..Our study demonstrates that rAAV-TFPI-2-mediated gene therapy offers a novel tool for the treatment of brain tumors...