Bioengineering 3-D Models for Breast Cancer Therapy

Summary

Principal Investigator: MINA JAHAN BISSELL
Abstract: The central objective of this proposal is to build 3D models of two epithelial cancers, lung and breast, which together cause more than 200,000 deaths each year in the U.S alone. The models will be used for 1- comparative analysis of how organ-specificity is maintained, a fundamental property that bears direct relevance to cancer progression and metastasis;2- determining whether responses to targeted therapies are organ-specific;and if so, 3- which components of the organ microenvironment may be causally involved in organ-specificity and therapeutic response. We hypothesize that inflammatory mediators, from immune cells as well as from resident myoepithelial, endothelial and activated stromal cells, contribute to tumor aggressiveness and resistance to targeted therapies. We will develop and utilize new biomaterials, substrata, defined media and markers for inclusion of immune, endothelial and normal- and cancer-derived stromal cells. This proposal brings together experts in cell, molecular and cancer biology and includes lung and breast oncologists, and investigators with expertise in imaging, tumor immunology, bioengineering, nanotechnology, materials science and computation. The 3 projects are as follows: I- To develop conditions for defining and maintaining endothelial cell phenotypes specific to normal and malignant breast and lung, and to define organ-specific responses of endothelial cells to models developed in II and III. II- To develop a 3D model for normal and malignant human bronchial epithelium, and to test the influence of inflammatory mediators. III- To build on the existing 3D models of the breast epithelium by incorporating other cell types and the effect of inflammatory microenvironments. All projects will test a number of targeted therapeutics, some of which are new and provided by our collaborators. Data quality control will be ensured since all projects will work through a virtual core to standardize cell culture and reagent development, and validate measurements of markers'and cellular responses. The creation of a physiological milieu will aid in understanding how these two different organs respond to, and interact with, their respective microenvironments. Moreover, elucidating similarities and differences in breast and airway epithelium will facilitate discovery and design of novel tissue-specific therapies.
Funding Period: ----------------2006 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc The tumor microenvironment modulates tamoxifen resistance in breast cancer: a role for soluble stromal factors and fibronectin through β1 integrin
    Osvaldo Pontiggia
    Area de Investigaciones, Instituto de Oncologia Angel H Roffo, Buenos Aires, Argentina
    Breast Cancer Res Treat 133:459-71. 2012
  2. pmc Deficiency of the p53/p63 target Perp alters mammary gland homeostasis and promotes cancer
    Rachel L Dusek
    Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Center for Clinical Sciences Research Room 1255, 269 Campus Drive, Stanford, CA 94305, USA
    Breast Cancer Res 14:R65. 2012
  3. pmc MYC suppresses cancer metastasis by direct transcriptional silencing of αv and β3 integrin subunits
    Hong Liu
    G W Hooper Foundation, University of California at San Francisco, San Francisco, California 94143, USA
    Nat Cell Biol 14:567-74. 2012
  4. pmc An "elite hacker": breast tumors exploit the normal microenvironment program to instruct their progression and biological diversity
    Aaron Boudreau
    Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
    Cell Adh Migr 6:236-48. 2012
  5. pmc FAM83A confers EGFR-TKI resistance in breast cancer cells and in mice
    Sun Young Lee
    Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    J Clin Invest 122:3211-20. 2012
  6. pmc Isolation and expansion of endothelial progenitor cells derived from mouse embryonic stem cells
    S Bahram Bahrami
    Department of Surgery, University of California San Francisco, San Francisco, CA, USA
    Methods Mol Biol 916:81-96. 2012
  7. pmc Three-dimensional culture of human breast epithelial cells: the how and the why
    Pierre Alexandre Vidi
    Department of Basic Medical Sciences and Center for Cancer Research, Purdue University, West Lafayette, IN, USA
    Methods Mol Biol 945:193-219. 2013
  8. pmc Splicing program of human MENA produces a previously undescribed isoform associated with invasive, mesenchymal-like breast tumors
    Francesca Di Modugno
    Department of Experimental Oncology, Regina Elena National Cancer Institute, 00158 Rome, Italy
    Proc Natl Acad Sci U S A 109:19280-5. 2012
  9. pmc Patterned collagen fibers orient branching mammary epithelium through distinct signaling modules
    Douglas G Brownfield
    Department of Bioengineering, University of California Berkeley, Berkeley, CA 94720, USA
    Curr Biol 23:703-9. 2013
  10. pmc The hemopexin domain of MMP3 is responsible for mammary epithelial invasion and morphogenesis through extracellular interaction with HSP90β
    Ana Luísa Correia
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Genes Dev 27:805-17. 2013

Scientific Experts

  • Virginia A Spencer
  • Kandice Tanner
  • Kristin Andersen
  • M J Bissell
  • Marcia V Fournier
  • Cyrus M Ghajar
  • Lone Rønnov-Jessen
  • Pierre Alexandre Vidi
  • Marina Simian
  • Hidetoshi Mori
  • Ren Xu
  • Britta Weigelt
  • Mandana Veiseh
  • Ana Luísa Correia
  • S Bahram Bahrami
  • Aaron Boudreau
  • Paraic A Kenny
  • Eva A Turley
  • Saori Furuta
  • Irene Kuhn
  • Mark A Labarge
  • Rana Mroue
  • Douglas G Brownfield
  • Jiyoung Kim
  • Sun Young Lee
  • Hong Liu
  • Francesca Di Modugno
  • Rachel L Dusek
  • Osvaldo Pontiggia
  • Alvin Lo
  • Emily I Chen
  • Nancy J Boudreau
  • Lea Chanson
  • Jordi Alcaraz
  • Derek C Radisky
  • Alain Beliveau
  • Jin Min Nam
  • Jamie L Inman
  • James Koropatnick
  • Amy Chen
  • Xueping Zhang
  • Katherine J Martin
  • Sara R Hamilton
  • Daniel A Fletcher
  • Gautham Venugopalan
  • Fernando C Schmitt
  • J Michael Bishop
  • Pierluigi Iapicca
  • Paola Nistico
  • Roland Meier
  • Therese Sørlie
  • Russ P Carstens
  • Laura D Attardi
  • Daniel Breadner
  • Signe Z Grønlund
  • Rocio Sampayo
  • Elisa Bal de Kier Joffé
  • Diego Raffo
  • Hannes Vogel
  • Paul A W Edwards
  • Alexander D Borowsky
  • David Mikilus
  • Natalia Akentieva
  • Jamie L Bascom
  • Marcella Mottolese
  • Agla J Fridriksdottir
  • Ting Yim Lee
  • Rashmin C Savani
  • Dun Yang
  • Laura J Van't Veer
  • Vera Timmermans Wielenga
  • Fritz Rank
  • Anne Lise Børresen-Dale
  • Irene Terrenato
  • Lisa Collis
  • Marc E Lenburg
  • Stefan Gustafson
  • Leonard G Luyt
  • Rene Harrison
  • Ole William Petersen
  • Angela Santoni
  • Hiroko Solvang
  • Sylvain Baron
  • Louise Fogh
  • Letizia Perracchio
  • Jenny Ma
  • Andrea Motter
  • Rene Villadsen
  • Evette S Radisky
  • Wen Hwa Lee

Detail Information

Publications49

  1. pmc The tumor microenvironment modulates tamoxifen resistance in breast cancer: a role for soluble stromal factors and fibronectin through β1 integrin
    Osvaldo Pontiggia
    Area de Investigaciones, Instituto de Oncologia Angel H Roffo, Buenos Aires, Argentina
    Breast Cancer Res Treat 133:459-71. 2012
    ..Our results show that the tumor microenvironment can modulate tamoxifen resistance, providing an alternative explanation for why patients become refractory to hormone-therapy...
  2. pmc Deficiency of the p53/p63 target Perp alters mammary gland homeostasis and promotes cancer
    Rachel L Dusek
    Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Center for Clinical Sciences Research Room 1255, 269 Campus Drive, Stanford, CA 94305, USA
    Breast Cancer Res 14:R65. 2012
    ..Given that p63 is essential for proper mammary gland development and that cell adhesion is fundamental for ensuring the proper architecture and function of the mammary epithelium, here we investigate Perp function in the mammary gland...
  3. pmc MYC suppresses cancer metastasis by direct transcriptional silencing of αv and β3 integrin subunits
    Hong Liu
    G W Hooper Foundation, University of California at San Francisco, San Francisco, California 94143, USA
    Nat Cell Biol 14:567-74. 2012
    ....
  4. pmc An "elite hacker": breast tumors exploit the normal microenvironment program to instruct their progression and biological diversity
    Aaron Boudreau
    Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
    Cell Adh Migr 6:236-48. 2012
    ....
  5. pmc FAM83A confers EGFR-TKI resistance in breast cancer cells and in mice
    Sun Young Lee
    Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    J Clin Invest 122:3211-20. 2012
    ..We found that FAM83A interacted with and caused phosphorylation of c-RAF and PI3K p85, upstream of MAPK and downstream of EGFR. These data provide an additional mechanism by which tumor cells can become EGFR-TKI resistant...
  6. pmc Isolation and expansion of endothelial progenitor cells derived from mouse embryonic stem cells
    S Bahram Bahrami
    Department of Surgery, University of California San Francisco, San Francisco, CA, USA
    Methods Mol Biol 916:81-96. 2012
    ..1 % gelatin-coated plates. The differentiated cells can be analyzed by real-time PCR and flow cytometry to confirm enrichment of EC-specific genes and proteins...
  7. pmc Three-dimensional culture of human breast epithelial cells: the how and the why
    Pierre Alexandre Vidi
    Department of Basic Medical Sciences and Center for Cancer Research, Purdue University, West Lafayette, IN, USA
    Methods Mol Biol 945:193-219. 2013
    ..We believe that using 3D cultures is an indispensable method to unravel the intricacies of human mammary functions and would best serve the fight against breast cancer...
  8. pmc Splicing program of human MENA produces a previously undescribed isoform associated with invasive, mesenchymal-like breast tumors
    Francesca Di Modugno
    Department of Experimental Oncology, Regina Elena National Cancer Institute, 00158 Rome, Italy
    Proc Natl Acad Sci U S A 109:19280-5. 2012
    ..These data suggest that polarized and growth-arrested cellular architecture correlates with absence of alternative hMENA isoform expression, and that the hMENA splicing program is relevant to malignant progression in invasive disease...
  9. pmc Patterned collagen fibers orient branching mammary epithelium through distinct signaling modules
    Douglas G Brownfield
    Department of Bioengineering, University of California Berkeley, Berkeley, CA 94720, USA
    Curr Biol 23:703-9. 2013
    ..Our data provide an explanation for how the stromal ECM encodes architectural cues for branch orientation as well as how the branching epithelium interprets and reinforces these cues through distinct signaling processes...
  10. pmc The hemopexin domain of MMP3 is responsible for mammary epithelial invasion and morphogenesis through extracellular interaction with HSP90β
    Ana Luísa Correia
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Genes Dev 27:805-17. 2013
    ..Our data also may shed light on the failure of strategies to use MMP inhibitors in cancer treatment and other related disorders...
  11. pmc The perivascular niche regulates breast tumour dormancy
    Cyrus M Ghajar
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Nat Cell Biol 15:807-17. 2013
    ..Our work reveals that stable microvasculature constitutes a dormant niche, whereas sprouting neovasculature sparks micrometastatic outgrowth. ..
  12. pmc Three-dimensional cultures of mouse mammary epithelial cells
    Rana Mroue
    Lawrence Berkeley National Laboratory, Berkeley, CA, USA
    Methods Mol Biol 945:221-50. 2013
    ..Finally we also discuss how advances in bioengineering tools may help towards the ultimate goal of building tissues and organs in culture for basic research and clinical studies...
  13. pmc Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets
    Katherine J Martin
    Bioarray Consulting, Belmont, Massachusetts, United States of America
    PLoS ONE 3:e2994. 2008
    ..Here we examine the ability of this gene signature (3D-signature) to predict prognosis in three independent breast cancer microarray datasets having 295, 286, and 118 samples, respectively...
  14. pmc Modelling molecular mechanisms of breast cancer and invasion: lessons from the normal gland
    M J Bissell
    Division of Life Sciences, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA
    Biochem Soc Trans 35:18-22. 2007
    ....
  15. pmc The hyaluronan receptors CD44 and Rhamm (CD168) form complexes with ERK1,2 that sustain high basal motility in breast cancer cells
    Sara R Hamilton
    London Regional Cancer Program, London Health Sciences Centre, and the University of Western Ontario, London, and Department of Cardiovascular Research, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
    J Biol Chem 282:16667-80. 2007
    ..Therefore, an effect of CD44 on tumor cell motility may depend in part on its ability to partner with additional proteins, such as cell surface Rhamm...
  16. pmc Mechanisms of disease: epithelial-mesenchymal transition--does cellular plasticity fuel neoplastic progression?
    Eva A Turley
    London Health Sciences Centre, University of Western Ontario, London, ON, Canada
    Nat Clin Pract Oncol 5:280-90. 2008
    ..We also highlight the role of RAS-controlled signaling mediators, ERK1, ERK2 and phosphatidylinositol 3-kinase, as microenvironmental responsive regulators of EMT...
  17. pmc Unraveling the microenvironmental influences on the normal mammary gland and breast cancer
    Britta Weigelt
    Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 977 225A, Berkeley, CA 94720, USA
    Semin Cancer Biol 18:311-21. 2008
    ....
  18. pmc Is CD133 a marker of metastatic colon cancer stem cells?
    Mark A Labarge
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    J Clin Invest 118:2021-4. 2008
    ..In light of these new findings, the popular notion that CD133 is a marker of colon CSCs may need to be revised...
  19. pmc The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression
    Paraic A Kenny
    Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA
    Mol Oncol 1:84-96. 2007
    ..We further demonstrate that consistent differences in genes encoding signal transduction proteins emerge when even tumor cells are cultured in 3D microenvironments...
  20. pmc Extracellular matrix control of mammary gland morphogenesis and tumorigenesis: insights from imaging
    Cyrus M Ghajar
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 8206, USA
    Histochem Cell Biol 130:1105-18. 2008
    ....
  21. pmc Endothelial cell migration and vascular endothelial growth factor expression are the result of loss of breast tissue polarity
    Amy Chen
    Department of Surgery, University of California at San Francisco, 94143, USA
    Cancer Res 69:6721-9. 2009
    ..These data confirm the importance of tissue architecture and polarity in malignant progression...
  22. pmc Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity
    Jiyoung Kim
    Department of Cellular and Molecular Medicine, Centre for Biological Disease Analysis and Danish Stem Cell Centre, Faculty of Health Sciences, University of Copenhagen, DK 2200 Copenhagen N, Denmark
    Proc Natl Acad Sci U S A 109:6124-9. 2012
    ....
  23. pmc The tumor microenvironment is a dominant force in multidrug resistance
    Ana Luísa Correia
    Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 977, Berkeley, CA 94720, USA
    Drug Resist Updat 15:39-49. 2012
    ..Targeting this dynamic interplay could be considered a new avenue to prevent therapeutic resistance, and may even provide a promising effective cancer treatment...
  24. pmc Interaction of E-cadherin and PTEN regulates morphogenesis and growth arrest in human mammary epithelial cells
    Marcia V Fournier
    Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Cancer Res 69:4545-52. 2009
    ..This interaction thus seems to be a critical integrator of proliferative and morphogenetic signaling in breast epithelial cells...
  25. pmc Inhibition of vimentin or beta1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo
    Xueping Zhang
    Department of Biochemistry and Molecular Biology, Virginia Commonwealth University Medical Campus, P O Box 980614, Richmond, VA 23298 0614, USA
    Mol Cancer Ther 8:499-508. 2009
    ..These studies suggest that the levels of vimentin and beta1 integrin play a key role in the homeostasis of the normal acinus in prostate and that their dysregulation may lead to tumorigenesis...
  26. pmc Breast cancer by proxy: can the microenvironment be both the cause and consequence?
    Lone Rønnov-Jessen
    Department of Biology, University of Copenhagen, Universitetsparken 13, DK 2100 Copenhagen, Denmark
    Trends Mol Med 15:5-13. 2009
    ..As such, the tumor microenvironment and its constituents, alone or in combination, might serve as promising targets for therapy...
  27. pmc Estrogen and progesterone receptors have distinct roles in the establishment of the hyperplastic phenotype in PR-A transgenic mice
    Marina Simian
    Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
    Breast Cancer Res 11:R72. 2009
    ..Our objective was to determine the roles of estrogen (E) and progesterone (P) in the genesis of mammary hyperplasias/preneoplasias in PR-A transgenics...
  28. pmc Temporal changes in Hox gene expression accompany endothelial cell differentiation of embryonic stem cells
    S Bahram Bahrami
    Department of Surgery University of California San Francisco, CA, USA
    Cell Adh Migr 5:133-41. 2011
    ....
  29. pmc Interconnected contribution of tissue morphogenesis and the nuclear protein NuMA to the DNA damage response
    Pierre Alexandre Vidi
    Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA
    J Cell Sci 125:350-61. 2012
    ..This is shown using high-content analysis of nuclear morphometric descriptors. Furthermore, silencing NuMA impairs H2AX phosphorylation--thus, tissue polarity and NuMA cooperate to maintain genome integrity...
  30. pmc Coherent angular motion in the establishment of multicellular architecture of glandular tissues
    Kandice Tanner
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 109:1973-8. 2012
    ..We propose that CAMo is an integral step in the formation of the tissue architecture and that its disruption is involved in malignant transformation...
  31. pmc Imaging of homeostatic, neoplastic, and injured tissues by HA-based probes
    Mandana Veiseh
    Division of Life Sciences, Lawrence Berkeley National Laboratories, Berkeley, California, USA
    Biomacromolecules 13:12-22. 2012
    ..Our results suggest that HA-based probes, which do not require polysaccharide backbone modification to achieve favorable half-life and distribution, can detect elevated HA metabolism in homeostatic, injured, and diseased tissues...
  32. pmc Apical polarity in three-dimensional culture systems: where to now?
    Jamie L Inman
    Lawrence Berkeley National Laboratory, Division of Life Sciences, 1 Cyclotron Road, Berkeley, CA 94720, USA
    J Biol 9:2. 2010
    ....
  33. pmc Gene expression in the third dimension: the ECM-nucleus connection
    Virginia A Spencer
    Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 977R225A, Berkeley, CA 94720, USA
    J Mammary Gland Biol Neoplasia 15:65-71. 2010
    ....
  34. pmc Tumor engineering: the other face of tissue engineering
    Cyrus M Ghajar
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 8206, USA
    Tissue Eng Part A 16:2153-6. 2010
    ....
  35. pmc Breast cancer cells in three-dimensional culture display an enhanced radioresponse after coordinate targeting of integrin alpha5beta1 and fibronectin
    Jin Min Nam
    Life Sciences Division, Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, California, USA
    Cancer Res 70:5238-48. 2010
    ..Our findings offer preclinical validation of fibronectin and alpha5beta1-integrin as targets for breast cancer therapy...
  36. pmc Laminin regulates PI3K basal localization and activation to sustain STAT5 activation
    Ren Xu
    Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, USA
    Cell Cycle 9:4315-22. 2010
    ..These results indicate that PI3K is a key mediator of the LN1-induced signaling cascade which controls the activity of transcription factors essential for tissue-specific gene expression...
  37. pmc Dissecting regional variations in stress fiber mechanics in living cells with laser nanosurgery
    Kandice Tanner
    Lawrence Berkeley National Laboratory, University of California, Berkeley, California, USA
    Biophys J 99:2775-83. 2010
    ..They also suggest that some fibers can absorb components and assume mechanical roles of other fibers to stabilize cell shape...
  38. pmc Raf-induced MMP9 disrupts tissue architecture of human breast cells in three-dimensional culture and is necessary for tumor growth in vivo
    Alain Beliveau
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Genes Dev 24:2800-11. 2010
    ....
  39. pmc Depletion of nuclear actin is a key mediator of quiescence in epithelial cells
    Virginia A Spencer
    Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 977R225A, Berkeley, CA 94720, USA
    J Cell Sci 124:123-32. 2011
    ..These data indicate a novel role for nuclear β-actin in growth arrest of epithelial cells and underscore the importance of the integrity of the basement membrane in homeostasis...
  40. pmc The metastasis-promoting protein S100A4 regulates mammary branching morphogenesis
    Kristin Andersen
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
    Dev Biol 352:181-90. 2011
    ..We suggest that S100A4-mediated effects during branching morphogenesis provide a plausible mechanism for how it may function in breast cancer progression...
  41. pmc Self-organization of engineered epithelial tubules by differential cellular motility
    Hidetoshi Mori
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 106:14890-5. 2009
    ..These results indicate that differential directional persistence can give rise to patterns within model developing tissues...
  42. pmc Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells
    Lea Chanson
    Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    Proc Natl Acad Sci U S A 108:3264-9. 2011
    ..Together these data show that self-organization is an innate and reversible property of communities of normal adult human mammary epithelial cells...
  43. pmc Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression
    Mina J Bissell
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA
    Nat Med 17:320-9. 2011
    ..We also include a discussion of how this information is being tailored for clinical use...
  44. pmc IL-25 causes apoptosis of IL-25R-expressing breast cancer cells without toxicity to nonmalignant cells
    Saori Furuta
    Department of Biological Chemistry, College of Medicine, University of California, Irvine, CA 92697, USA
    Sci Transl Med 3:78ra31. 2011
    ..In response to IL-25, the IL-25R on the surface of breast cancer cells activated caspase-mediated apoptosis. Thus, the IL-25/IL-25R signaling pathway may serve as a new therapeutic target for advanced breast cancer...
  45. pmc HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment
    Britta Weigelt
    Life Sciences Division, Lawrence Berkeley National Laboratory, University of California Berkeley, Mailstop 977R225A, 1 Cyclotron Road, Berkeley, CA 94720, USA
    Breast Cancer Res Treat 122:35-43. 2010
    ....
  46. pmc Collective epithelial cell invasion overcomes mechanical barriers of collagenous extracellular matrix by a narrow tube-like geometry and MMP14-dependent local softening
    Jordi Alcaraz
    Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 977R225A, Berkeley, CA 94720, USA
    Integr Biol (Camb) 3:1153-66. 2011
    ....
  47. pmc Laser scanning-based tissue autofluorescence/fluorescence imaging (LS-TAFI), a new technique for analysis of microanatomy in whole-mount tissues
    Hidetoshi Mori
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Am J Pathol 180:2249-56. 2012
    ..This technique could be useful for rapid diagnosis of human clinical samples and possibly the effect of subtle variations such as low dose radiation...