Ramsey A. Foty Assistant Professor UMDNJ Department of Surgery Clinical Academic Building Room 7070 125 Paterson Street New Brunswick. NJ 08903 (732) 235-7482 fotyra@umdnj.edu

The biophysical and biomolecular basis of prostate cancer progression to metastasis

Prostate cancer is a major health concern in the U.S. Its metastatic phenotype is the major source of its morbidity and mortality. Two essential pre-requisites for the transition of prostate cancer from a curable. organ-confined lesion into a malignant and therapy-resistant disease are detachment of cells from the tumor and preferential association of tumor cells with bone. These two processes are strongly influenced by cell-cell cohesion and cell-substratum adhesion. attributes that impart to tumors quantifiable biophysical properties. These properties are tumor elasticity (a measure of a tumors' ability to deform in response to an applied stress). tumor viscosity (an indication of cellular motility within the tumor). and tumor cohesivity (a dynamic and complex manifestation of cell-cell cohesion and cell-substratum adhesion).

Our lab has developed a novel in vitro method. tissue surface tensiometry (TST). to simultaneously measure these properties. and are applying TST to investigate the biophysical and biomolecular changes accompanying the malignant progression of prostate cancer. Ongoing projects in our lab include a) assessment of the efficacy of tissue surface tensiometry as an accurate predictor of the invasive and metastatic potential of prostate tumors. b) exploration of how changes in various key molecular and cellular components underlying cell-cell cohesivity and cell-substratum adhesivity influence the elasticoviscous and cohesive properties of the tumor. and c) employment of a novel in vitro organotropism assay to address key issues regarding dissemination to bone of human prostate cancer cells.

Selected Publications

Jia D, Dajusta D, Foty RA. (2007) Tissue surface tensions guide in vitro self-assembly of rodent pancreatic islet cells. Dev Dyn. 236(8):2039-49.

Winters, B.S., Mohan Raj, B.K.,Robinson, E.E., Foty, R.A., and Corbett, S.A.(2006) Three-dimensional Culture Regulates Raf-1 Expression to Modulate Fibronectin Matrix Assembly. Molecular Biology of the Cell 17:3386-3396.

Perez-Pomares, J.M. and R. A. Foty (2006). Tissue fusion and cell sorting in embryonic development and disease: biomedical implications. Bioessays 28:809-821.

Yang JM. O'Neill P. Jin W. Foty R. Medina DJ. Xu Z. Lomas M. Arndt GM. Tang Y. Nakada M. Yan L. Hait WN. (2006) Extracellular matrix metalloproteinase inducer (CD147) confers resistance of breast cancer cells to Anoikis through inhibition of Bim. J Biol Chem. 281(14):9719-27.

Foty RA. Steinberg MS. (2005) The differential adhesion hypothesis: a direct evaluation. Dev Biol. 278(1):255-63.

Winters BS. Shepard SR. Foty RA. (2005) Biophysical measurement of brain tumor cohesion. Int J Cancer. 114(3):371-9.

Robinson. E.. Foty. R. and Corbertt. S. (2004). Fibronectin matrix assembly regulates a5b1 integrin mediated cell cohesion. Mol. Biol. Cell 15:973-981.

Forgacs. G. and R. Foty (2004). Biological relevance of tissue liquidity and viscoelasticity. Function and regulation of cellular systems: Experiments and models. A. Deutsch. J. Howard. M. Falcke and W. Zimmerman. Editors. Birkhauser Pres. Boston. W269-277.

Foty. Ramsey A. and Malcolm S. Steinberg (2004). Cadherin-mediated cell-cell adhesion and tissue segregation in relation to malignancy. Int. J. Dev. Biol. 48:397-409.

Winters. B.S.. Scott R. Shepard and Ramsey A. Foty (2005). Biophysical measurement of brain tumor cohesion. Int. J. Cancer 114:371-379.

Foty. Ramsey A. and Malcolm S. Steinberg (2005). The Differential Adhesion Hypothesis: a direct evaluation. Dev. Biol. 278(1):255-263 .

Duguay. D.. Foty. R.A. and Steinberg. M.S. (2002). Qualtitative and quantitative determinants of cadherin-mediated cell sorting. Developmental Biology (in press).

Robinson. E.. Zazzali. K.. Corbertt. S. and Foty. R. (2002). a5b1 integrin mediates strong tissue cohesion. Journal of Cell Science (in press).

Ryan PL. Foty RA. Kohn J. Steinberg MS. (2001) Tissue spreading on implantable substrates is a competitive outcome of cell-cell vs. cell-substratum adhesivity. Proc Natl Acad Sci U S A 98:4323-7.

Foty RA. Corbett SA. Schwarzbauer JE. Steinberg MS. (1998) Dexamethasone up-regulates cadherin expression and cohesion of HT-1080 human fibrosarcoma cells. Cancer Res 58:3586-9.

Forgacs G. Foty RA. Shafrir Y. Steinberg MS. (1998) Viscoelastic properties of living embryonic tissues: a quantitative study. Biophys J 74:2227-34.