Microenvironmental Influences on Gene Expression and Tissue Specificity in Normal and Malignant Breast.
The laboratory is interested in the role of extracellular matrix (ECM), its receptors and its degrading enzymes as central modulators of tissue-specific gene expression, signal transduction, apoptosis and cancer. Given that all tissues share the same DNA sequences, the question of how tissue specificity is maintained and how it goes awry in cancer is a central problem in biology. Our laboratory has developed "designer microenvironments" in three-dimensional (3D) cultures to study the role of the microenvironment and tissue architecture in normal and malignant cells and how these external factors shape signal transduction in tissues. We show that non-malignant and malignant mammary cells isolated from either human or mouse can be distinguished rapidly and unequivocally in our 3D assays. We can revert the malignant phenotype if the structure is restored in 3D. We also show that while all signal transduction pathways are integrated reciprocally in 3D, these pathways appear to be disconnected on tissue culture plastic (2D). Finally, we show that aberration in microenvironmental control or loss of ECM can lead to genomic instability. We conclude that the structure of the tissue is dominant over the genome and that we may need a new paradigm for how tissue-specific genes are regulated in vivo.
The laboratory is also engaged in the studies of branching morphogenesis in the mammary gland, with specific emphasis on the role of ECM, its degrading enzymes (MMPs) and the morphogen, epimorphin (syntaxin 2). Finally, we are also developing theoretical models of signal transduction in 3D tissues. The laboratory comprises a multidisciplinary group of scientists, postdoctoral fellows and graduate students (biologists, bioinformaticists, bioengineers, physicists). We collaborate closely with the laboratories of Professors Ole W. Petersen (The Panum Institute, University of Copenhagen, Denmark) and Zena Werb (Department of Anatomy, University of California, San Francisco) as well as a number of other investigators here at LBNL and on the University of California, Berkeley campus. Please see the selected literatures and also visit the Bissell Laboratory Website
Total publications: 339 (as of 4/13/11)
Complete Publications List (PDF) here.
13. Bissell MJ, Rambeck WA, White RC and Bassham JA. (1976) Glycerol phosphate shuttle in virus-transformed cells in culture. Science 191:856-858.
21. Teng M-H, Bartholomew J and Bissell MJ. (1977) Synergism between anti-microtubule agents and growth stimulants in enhancement of cell cycle traverse. Nature 268:739-741.
49. Bissell MJ, Hall HG and Parry G. (1982) How does extracellular matrix direct gene expression? J Theor Biol 99:31-68.
54. Dolberg DS and Bissell MJ. (1984) Inability of Rous sarcoma virus to cause sarcomas in the avian embryo. Nature 309:552-556.
60. Dolberg DS, Hollingsworth R, Hertle M and Bissell MJ. (1985) Wounding and its role in RSV-induced tumor formation. Science 230:676-678.
96. Sieweke MH, Thompson NL, Sporn MB and Bissell MJ. (1990) Mediation of wound-related Rous sarcoma virus tumorigenesis by TGF-ß. Science 248:1656-1660.
105. Streuli CH, Bailey N and Bissell MJ. (1991) Control of mammary epithelial differentiation: Basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity. J Cell Biol. 115:1383-95. [Selected as one of the 40 Landmark Papers in Cell Biology in the past 50 years (Joseph G. Gall and J. Richard McIntosh, eds.). pp. 336-348 (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, and the American Society for Cell Biology, Bethesda, MD.]
113. Petersen OW, Rønnov–Jessen L, Howlett AR and Bissell MJ (1992). Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc Natl Acad Sci USA. 1992 Oct 1; 89(19):9064–8.
140. Boudreau N, Sympson CJ, Werb Z and Bissell MJ. (1995) Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix. Science 267:891-893.
166. Weaver VM, Petersen OW, Wang F, Larabell CA, Briand P, Damsky C and Bissell MJ. (1997) Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo using integrin blocking antibodies. J Cell Biol 137:231-246 (cover).
167. Lochter A, Galosy S, Muschler J, Freedman N, Werb Z and Bissell MJ. (1997) Matrix metalloproteinase stromelysin-1 triggers a cascade of molecular alterations that leads to stable epithelial-to-mesenchymal conversion and a premalignant phenotype in mammary epithelial cells. J Cell Biol 139:1861-1872.
171. Myers CA, Schmidhauser C, Mellentin-Michelotti J, Fragoso G, Roskelley CD, Casperson G, Mossi R, Pujuguet P, Hager G and Bissell MJ. (1998) Characterization of BCE-1: A transcriptional enhancer regulated by prolactin and extracellular matrix and modulated by the state of histone acetylation. Mol Cell Biol 18(4):2184-2195.
189. Sternlicht MD, Lochter A, Sympson CJ, Huey B, Rougier J-P, Gray J, Pinkel D, + Bissell MJ and + Werb Z. (1999) The stromal proteinase MMP-3/stromelysin-1 promotes mammary carcinogenesis. Cell 98(2):137-46. (+ The two laboratories contributed equally to this work.)
214. Weaver VM, Lelièvre SA, Lakins JN, Chrenek MA, Jones JCR, Giancotti F, Werb Z and Bissell MJ. (2002) b4 Integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell2:205-216. Also see Nature (News & Views) 419:790-791 and MiniReview (Cell) 111:923-925 (2002).
253. Radisky DC, Levy DD, Littlepage LE, Liu H, Nelson CM, Fata JE, Leake D, Godden EL, Albertson DG, Nieto MA, Werb Z and Bissell MJ (2005). Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436(7047):123-7.
268. Nelson CM, VanDuijn MM, Inman JL, Fletcher DA and Bissell MJ (2006). Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures. Science. 2006 Oct 13; 314(5797):298–300.
274. Kenny PA and Bissell MJ (2007). Targeting TACE-dependent EGFR ligand shedding in breast cancer. J Clin Invest. 2007 Feb; 117(2):337–45.
291. Rizki A, Weaver VM, Lee SY, Rozenberg GI, Chin K, Myers CA, Bascom JL, Mott JD, Semeiks JR, Grate LR, Mian IS, Borowsky AD, Jensen RA, Idowu MO, Chen F, Chen DJ, Petersen OW, Gray JW and Bissell MJ (2008). A human breast cell model of preinvasive to invasive transition. Cancer Res. 2008 Mar 1; 68(5):1378–87 (cover highlight).
307. LaBarge MA, Nelson CM, Villadsen R, Fridriksdottir A, Ruth JR, Stampfer M, Petersen OW and Bissell MJ (2009). Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments. Integr Biol. 2009 Jan; 1:70–9.
328. Beliveau A, Mott JD, Lo A, Chen EI, Koller AA, Yaswen P, Muschler J and Bissell MJ (2010). Raf-induced MMP9 Disrupts Tissue Architecture of Human Breast Cells in Three-Dimensional Culture and is Necessary for Tumor Growth in vivo. Genes Dev. 2010 Dec 15;24(24):2800-11.
332. Bissell MJ and Hines, WC (2011). Why do we get so few tumors?! A proposed role of the microenvironment in restraining cancer progression. Nat Med. 2011. Mar; 17(3): 320-9.