Genomes and Genes
Summary: A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-.
- Hopps E, Lo Presti R, Montana M, Noto D, Averna M, Caimi G. Gelatinases and their tissue inhibitors in a group of subjects with metabolic syndrome. J Investig Med. 2013;61:978-83 pubmed publisher..An altered pattern of MMPs and their inhibitors is demonstrated in MS; the presence of diabetes mellitus strongly influences the concentration of MMP and TIMP, contributing probably to the increased cardiovascular risk of MS subjects. ..
- Jacob M, Chang L, Pure E. Fibroblast activation protein in remodeling tissues. Curr Mol Med. 2012;12:1220-43 pubmed..Finally, we discuss the potential risks and therapeutic benefits of targeting FAP and FAP-expressing cells, as well as approaches to do so. ..
- Liu Q, Li R, Qian H, Yang M, Zhu Z, Wu W, et al. Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(?-caprolactone) nanoparticles. Int J Nanomedicine. 2012;7:281-95 pubmed publisher..We found clear evidence that the DOC-TNPs were transformed by gelatinases, allowing drug release and enhancing the cellular uptake of DOC (P < 0.01)...
- Zhou T, Qin Y, Lei F, Su L, Zhao Y, Huang W. Less gelatinases is associated with apolipoprotein E accumulation in glomerulosclerosis rats. Histol Histopathol. 2012;27:249-56 pubmed publisherb>Gelatinases include matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The abnormal expressions of gelatinases are implicated in the pathogenesis of extracellular matrix (ECM) accumulation...
- Claramunt R, Bouissane L, Cabildo M, Cornago M, Elguero J, Radziwon A, et al. Synthesis and biological evaluation of curcuminoid pyrazoles as new therapeutic agents in inflammatory bowel disease: effect on matrix metalloproteinases. Bioorg Med Chem. 2009;17:1290-6 pubmed publisher..Zymographic analysis revealed that three compounds significantly down-regulated MMP-9 activity on inflammation-induced intestinal epithelial cells, making them original candidates for the treatment of inflammatory bowel disease (IBD). ..
- Haschtmann D, Ferguson S, Stoyanov J. Apoptosis and gene expression of collagenases but not gelatinases in rabbit disc fragment cultures. J Neurosurg Spine. 2008;8:552-60 pubmed publisher..loss on histological studies, lactate dehydrogenase activity, apoptosis, gene expression of collagenases and gelatinases, and for proinflammatory (MCP-1, IL-8, and IL-6) and apoptosis-associated (TNF-alpha, Fas-L, and caspase 3) ..
- Ospelt C, Mertens J, Jungel A, Brentano F, Maciejewska Rodriguez H, Huber L, et al. Inhibition of fibroblast activation protein and dipeptidylpeptidase 4 increases cartilage invasion by rheumatoid arthritis synovial fibroblasts. Arthritis Rheum. 2010;62:1224-35 pubmed publisher..Our results indicate a central role for the serine protease activity of FAP and DPP-4/CD26 in protecting articular cartilage against invasion by synovial fibroblasts in RA. ..
- LeBeau A, Brennen W, Aggarwal S, Denmeade S. Targeting the cancer stroma with a fibroblast activation protein-activated promelittin protoxin. Mol Cancer Ther. 2009;8:1378-86 pubmed publisher..Intratumoral injection of an FAP-activated protoxin produced significant lysis and growth inhibition of human breast and prostate cancer xenografts with minimal toxicity to the host animal. ..
- Wang W, Shao R, Wu Q, Ke S, McMurray J, Lang F, et al. Targeting gelatinases with a near-infrared fluorescent cyclic His-Try-Gly-Phe peptide. Mol Imaging Biol. 2009;11:424-33 pubmed publisher..of the study is to synthesize and characterize near-infrared (NIR) fluorescence imaging probes targeted to gelatinases. A phage display-selected cyclic peptide containing the His-Try-Gly-Phe (HWGF) motif was used as the lead ..
- Huang Y, Simms A, Mazur A, Wang S, León N, Jones B, et al. Fibroblast activation protein-? promotes tumor growth and invasion of breast cancer cells through non-enzymatic functions. Clin Exp Metastasis. 2011;28:567-79 pubmed publisher..We conclude that the proteolytic activity of FAP participates in matrix degradation, but other functions of the protein stimulate increased tumor growth. ..
- Bae S, Park C, Son H, Ju H, Paik D, Jeon C, et al. Fibroblast activation protein alpha identifies mesenchymal stromal cells from human bone marrow. Br J Haematol. 2008;142:827-30 pubmed publisher..FAP immunoselection yielded homogeneous MSCs from cryopreserved bone marrow (BM). These results suggest that FAP serves as a surface protein marker that can singly define MSCs from BM and possibly from other sources. ..
- Cohen S, Alpaugh R, Palazzo I, Meropol N, Rogatko A, Xu Z, et al. Fibroblast activation protein and its relationship to clinical outcome in pancreatic adenocarcinoma. Pancreas. 2008;37:154-8 pubmed publisher..Higher FAP expression is associated with worse clinical outcome. The investigation of FAP inhibitors as a therapeutic strategy against pancreatic cancer should be considered. ..
- Qiu L, Zhou Y, Wang Q, Yang L, Liu H, Xu S, et al. Synthetic gelatinases inhibitor attenuates electromagnetic pulse-induced blood-brain barrier disruption by inhibiting gelatinases-mediated ZO-1 degradation in rats. Toxicology. 2011;285:31-8 pubmed publisher..Matrix metalloproteinases (MMPs), in particular gelatinases (MMP-2 and MMP-9), play a key role in degradation of tight junction proteins, are known mediators of BBB ..
- Prakobwong S, Pinlaor P, Charoensuk L, Khoontawad J, Yongvanit P, Hiraku Y, et al. The liver fluke Opisthorchis viverrini expresses nitric oxide synthase but not gelatinases. Parasitol Int. 2012;61:112-7 pubmed publisher..DNA damage and secrete Ras-related C3 botulinum toxin substrate (Rac)1, heme oxygenase (HO)-1, and gelatinases (matrix metalloproteinase (MMP)2 and MMP9). We evaluated whether these enzymes are expressed in O. viverrini...
- Santos A, Jung J, Aziz N, Kissil J, Pure E. Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice. J Clin Invest. 2009;119:3613-25 pubmed publisher..These data provide proof of principle that targeting stromal cell-mediated modifications of the tumor microenvironment may be an effective approach to treating epithelial-derived solid tumors. ..
- Wen Y, Wang C, Ma T, Li Z, Zhou L, Mu B, et al. Immunotherapy targeting fibroblast activation protein inhibits tumor growth and increases survival in a murine colon cancer model. Cancer Sci. 2010;101:2325-32 pubmed publisher..5-fold increase in lifespan and no significant pathology. These results suggest that FAP, a product preferentially expressed by TAF, could function as an effective tumor rejection antigen. ..
- Saigusa S, Toiyama Y, Tanaka K, Yokoe T, Okugawa Y, Fujikawa H, et al. Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy. Int J Oncol. 2011;38:655-63 pubmed publisher..In conclusion, FAP-? and SDF-1 expression was shown to be involved in tumor re-growth and recurrence in rectal cancer patients treated with pre-operative CRT. ..
- Dohi O, Ohtani H, Hatori M, Sato E, Hosaka M, Nagura H, et al. Histogenesis-specific expression of fibroblast activation protein and dipeptidylpeptidase-IV in human bone and soft tissue tumours. Histopathology. 2009;55:432-40 pubmed publisher..DPP-IV is also expressed in monocyte-macrophage lineage cells. ..
- Pavlaki M, Debeli K, Triantaphyllidou I, Klouras N, Giannopoulou E, Aletras A. A proposed mechanism for the inhibitory effect of the anticancer agent titanocene dichloride on tumour gelatinases and other proteolytic enzymes. J Biol Inorg Chem. 2009;14:947-57 pubmed publisher..In this article it is demonstrated that titanocene dichloride inhibits tumour gelatinases in a dose-dependent manner...
- Huang S, Fang R, Xu J, Qiu S, Zhang H, Du J, et al. Evaluation of the tumor targeting of a FAP?-based doxorubicin prodrug. J Drug Target. 2011;19:487-96 pubmed publisher..These findings suggest that such FAP?-based prodrug strategy is promising to achieve targeted delivery of antitumor agents. ..
- Citak E, Oguz A, Karadeniz C, Akyurek N. Role of gelatinases (MMP-2 and MMP-9), TIMP-1, vascular endothelial growth factor (VEGF), and microvessel density on the clinicopathological behavior of childhood non-Hodgkin lymphoma. Pediatr Hematol Oncol. 2008;25:55-66 pubmed publisher..53% vs. 100% respectively, p = .039). Neither gelatinases nor VEGF correlated with age, sex, disease stage, the occurrence of bulky disease, or extranodal disease...
- Aggarwal S, Brennen W, Kole T, Schneider E, Topaloglu O, Yates M, et al. Fibroblast activation protein peptide substrates identified from human collagen I derived gelatin cleavage sites. Biochemistry. 2008;47:1076-86 pubmed..On the basis of these results, the FAP consensus sequences are currently being evaluated as FAP-selective peptide carriers for incorporation into FAP-activated prodrugs. ..
- Zhou T, Qin Y. The potential mechanism for the different expressions of gelatinases induced by all-trans retinoic acid in different cells. J Recept Signal Transduct Res. 2012;32:129-33 pubmed publisherb>Gelatinases include matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The increased expressions of gelatinases are implicated in the pathogenesis of cell injury and cell death...
- Bonfil R, Sabbota A, Nabha S, Bernardo M, Dong Z, Meng H, et al. Inhibition of human prostate cancer growth, osteolysis and angiogenesis in a bone metastasis model by a novel mechanism-based selective gelatinase inhibitor. Int J Cancer. 2006;118:2721-6 pubmed..However, therapeutic options for treatment of PC bone metastasis are limited. Gelatinases are members of the matrix metalloproteinase (MMP) family and have been shown to play a key role in PC ..
- Konstas A, Koliakos G, Karabatsas C, Liakos P, Schlötzer Schrehardt U, Georgiadis N, et al. Latanoprost therapy reduces the levels of TGF beta 1 and gelatinases in the aqueous humour of patients with exfoliative glaucoma. Exp Eye Res. 2006;82:319-22 pubmed..A better understanding of its effect on the pathobiology of the disease may lead to its earlier use in the disease process to prevent progression from XFS to XFG. ..
- Narra K, Mullins S, Lee H, Strzemkowski Brun B, Magalong K, Christiansen V, et al. Phase II trial of single agent Val-boroPro (Talabostat) inhibiting Fibroblast Activation Protein in patients with metastatic colorectal cancer. Cancer Biol Ther. 2007;6:1691-9 pubmed..However it provides the initial proof-of-concept that physiologic inhibition of FAP activity can be accomplished in patients with colorectal cancer, and lays the groundwork for future studies targeting the tumor stroma. ..
- Yang S, Hsieh Y, Lue K, Chu S, Chang I, Lu K. Effects of nonsteroidal anti-inflammatory drugs on the expression of urokinase plasminogen activator and inhibitor and gelatinases in the early osteoarthritic knee of humans. Clin Biochem. 2008;41:109-16 pubmed..drugs (NSAIDs) on the expression of urokinase-type plasminogen activator (u-PA), PA inhibitor-1 (PAI-1) and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] in the early knee osteoarthritis (OA) of humans...
- Henry L, Lee H, Lee J, Klein Szanto A, Watts P, Ross E, et al. Clinical implications of fibroblast activation protein in patients with colon cancer. Clin Cancer Res. 2007;13:1736-41 pubmed..It also suggests that the effects of FAP inhibition should be investigated in earlier-stage tumors, given its high levels and potential effect earlier in the course of the disease. ..
- Takahashi I, Onodera K, Nishimura M, Mitnai H, Sasano Y, Mitani H. Expression of genes for gelatinases and tissue inhibitors of metalloproteinases in periodontal tissues during orthodontic tooth movement. J Mol Histol. 2006;37:333-42 pubmed..This altered pattern of gene expression may determine the rate and extent of remodeling of the collagenous ECM in periodontal tissues during orthodontic tooth movement. ..
- Pellikainen J, Ropponen K, Kataja V, Kellokoski J, Eskelinen M, Kosma V. Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis. Clin Cancer Res. 2004;10:7621-8 pubmed..Evaluation of MMP-9 expression seems to add valuable information on breast cancer prognosis. ..
- Abu El Asrar A, Struyf S, Descamps F, Al Obeidan S, Proost P, Van Damme J, et al. Chemokines and gelatinases in the aqueous humor of patients with active uveitis. Am J Ophthalmol. 2004;138:401-11 pubmed..of the chemokines CXCL10/IP-10, CXCL11/I-TAC, CXCL8/1L-8, CXCL6/GCP-2, CCL3/MIP-1alpha, and CCL18/PARC, and gelatinases A and B in uveitis. Prospective, experimental, case-control study...
- Aertgeerts K, Levin I, Shi L, Snell G, Jennings A, Prasad G, et al. Structural and kinetic analysis of the substrate specificity of human fibroblast activation protein alpha. J Biol Chem. 2005;280:19441-4 pubmed..Our data provide a clear understanding of the molecular determinants responsible for the substrate specificity and endopeptidase activity of FAPalpha. ..
- Cheng J, Valianou M, Canutescu A, Jaffe E, Lee H, Wang H, et al. Abrogation of fibroblast activation protein enzymatic activity attenuates tumor growth. Mol Cancer Ther. 2005;4:351-60 pubmed
- Yu X, Han Z. Matrix metalloproteinases in bone marrow: roles of gelatinases in physiological hematopoiesis and hematopoietic malignancies. Histol Histopathol. 2006;21:519-31 pubmed publisher..Furthermore, the preclinical studies on the role of synthetic MMP inhibitors in the treatment of hematological malignancies will be discussed. ..
- Mook O, Frederiks W, Van Noorden C. The role of gelatinases in colorectal cancer progression and metastasis. Biochim Biophys Acta. 2004;1705:69-89 pubmedVarious proteases are involved in cancer progression and metastasis. In particular, gelatinases, matrix metalloproteinase-2 (MMP-2) and MMP-9, have been implicated to play a role in colon cancer progression and metastasis in animal ..
- Dolznig H, Schweifer N, Puri C, Kraut N, Rettig W, Kerjaschki D, et al. Characterization of cancer stroma markers: in silico analysis of an mRNA expression database for fibroblast activation protein and endosialin. Cancer Immun. 2005;5:10 pubmed..Constructing databases from microdissected cancer tissues may be an essential step for tumor stroma-targeted therapies. ..
- Caruso R, Fina D, Peluso I, Fantini M, Tosti C, Del Vecchio Blanco G, et al. IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis. J Immunol. 2007;178:5957-65 pubmed..These data indicate that IL-21 is overexpressed in Hp-infected gastric mucosa where it could contribute to increased epithelial gelatinase production. ..
- Bauer S, Jendro M, Wadle A, Kleber S, Stenner F, Dinser R, et al. Fibroblast activation protein is expressed by rheumatoid myofibroblast-like synoviocytes. Arthritis Res Ther. 2006;8:R171 pubmed..Moreover, the specific expression pattern qualifies FAP as a therapeutic target for inhibiting the destructive potential of fibroblast-like synovial cells. ..
- Wang X, Yu D, McCaughan G, Gorrell M. Fibroblast activation protein increases apoptosis, cell adhesion, and migration by the LX-2 human stellate cell line. Hepatology. 2005;42:935-45 pubmed
- Creti R, Imperi M, Bertuccini L, Fabretti F, Orefici G, Di Rosa R, et al. Survey for virulence determinants among Enterococcus faecalis isolated from different sources. J Med Microbiol. 2004;53:13-20 pubmed..Generally, isolates from endocarditis, biliary stents and the environment were equipped with fewer virulence factors than isolates from other sources. UTI strains possessed the highest number of factors. ..
- Christiansen V, Jackson K, Lee K, McKee P. Effect of fibroblast activation protein and alpha2-antiplasmin cleaving enzyme on collagen types I, III, and IV. Arch Biochem Biophys. 2007;457:177-86 pubmed..We conclude that FAP works in synchrony with other proteinases to cleave partially degraded or denatured collagen I and III as ECM is excavated, and that derivative peptides might function to regulate malignant cell growth and motility. ..
- Tchougounova E, Lundequist A, Fajardo I, Winberg J, Abrink M, Pejler G. A key role for mast cell chymase in the activation of pro-matrix metalloprotease-9 and pro-matrix metalloprotease-2. J Biol Chem. 2005;280:9291-6 pubmed..The present study thus indicates a key role for mast cell chymase in the regulation of pro-MMP-2 and -9 activities. Moreover, the results suggest an important role for mast cell chymase in regulating connective tissue homeostasis. ..
- Loeffler M, Kruger J, Niethammer A, Reisfeld R. Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. J Clin Invest. 2006;116:1955-62 pubmed..This strategy opens a new venue for the combination of immuno- and chemotherapies. ..
- Sulda M, Abbott C, Hildebrandt M. DPIV/CD26 and FAP in cancer: a tale of contradictions. Adv Exp Med Biol. 2006;575:197-206 pubmed
- Edosada C, Quan C, Wiesmann C, Tran T, Sutherlin D, Reynolds M, et al. Selective inhibition of fibroblast activation protein protease based on dipeptide substrate specificity. J Biol Chem. 2006;281:7437-44 pubmed..These results identify Ac-Gly-BoroPro as a FAP-selective inhibitor and suggest that N-acyl-Gly-Pro-based inhibitors will allow testing of FAP as a therapeutic target. ..
- Ramirez Montagut T, Blachere N, Sviderskaya E, Bennett D, Rettig W, Garin Chesa P, et al. FAPalpha, a surface peptidase expressed during wound healing, is a tumor suppressor. Oncogene. 2004;23:5435-46 pubmed..These results show that expression of FAP is a tumor suppressor that abrogates tumorigenicity through regulation of cell growth and survival. ..
- Lee J, Fassnacht M, Nair S, Boczkowski D, Gilboa E. Tumor immunotherapy targeting fibroblast activation protein, a product expressed in tumor-associated fibroblasts. Cancer Res. 2005;65:11156-63 pubmed..The study suggests that FAP, a product which is preferentially expressed in tumor-associated fibroblasts, could function as a tumor rejection antigen in a broad range of cancers. ..
- Chen D, Kennedy A, Wang J, Zeng W, Zhao Q, Pearl M, et al. Activation of EDTA-resistant gelatinases in malignant human tumors. Cancer Res. 2006;66:9977-85 pubmed..To test if activation of gelatinases associated with seprase could be involved in malignant tumors, we used a mammalian expression system to ..
- Gimeno Garcia A, Santana Rodríguez A, Jimenez A, Parra Blanco A, Nicolas Perez D, Paz Cabrera C, et al. Up-regulation of gelatinases in the colorectal adenoma-carcinoma sequence. Eur J Cancer. 2006;42:3246-52 pubmed..The present study demonstrates that MMP-9 is markedly up-regulated in the adenomatous tissue and suggests that this gelatinase might be a marker for early colorectal carcinogenesis. ..
- Frederiks W, Mook O. Metabolic mapping of proteinase activity with emphasis on in situ zymography of gelatinases: review and protocols. J Histochem Cytochem. 2004;52:711-22 pubmed..In that case, in situ zymography provides data that extend our understanding of the role of specific proteinases in various physiological and pathological conditions. ..
- Bauer S, Adrian N, Williamson B, Panousis C, Fadle N, Smerd J, et al. Targeted bioactivity of membrane-anchored TNF by an antibody-derived TNF fusion protein. J Immunol. 2004;172:3930-9 pubmed..These data warrant transfer of the anti-FAP-TNF immunocytokine into clinical trials for the treatment of FAP-positive tumors. ..