The desmoplastic response to tumor invasion is a poorly understood host myofibroblast-mediated collagenous response responsible for the """"""""hard lump"""""""" appearance of many human cancers. This competitive renewal will continue to study both the pathogenesis of the response as well as the effects of the response on tumor invasion and metastasis. The first basic aim will be to further characterize and purify the 25,000 M.W. myofibroblast growth factor, compare it to known growth factors, demonstrate a role for this factor in the pathogenesis of the response with in vivo studies of myofibroblast expression of c-myc, c-fos, elastin, Type I, and Type V collagen genes and will in vivo studies with the desmoplasia-inducing c-Has-ras transfected high p21 MCF-7 human breast carcinoma cell line. The second basic aim will be to study the role of the 40,000 M.W. desmoplastic inhibitor of metalloproteinases (DIMP) in conferring to the desmopastic response a partial but not total resistance to tumor invasion and metastasis. This will involve a detailed comparison of DIMP with TIMP (tissue inhibitor of metalloproteinases) and an evaluation of a possible mechanism which would allow successful tumor collagenolysis even whether the desmoplastic response, being only partially successful in inhibiting invasion, ultimately exerts selection pressure for subpopulations of the primary tumor with increased metastatic potential.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Pathology B Study Section (PTHB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Schools of Medicine
Los Angeles
United States
Zip Code
Mahooti, Sepi; Porter, Kyle; Alpaugh, Mary L et al. (2010) Breast carcinomatous tumoral emboli can result from encircling lymphovasculogenesis rather than lymphovascular invasion. Oncotarget 1:131-47
Barsky, Sanford H; Karlin, Nina J (2006) Mechanisms of disease: breast tumor pathogenesis and the role of the myoepithelial cell. Nat Clin Pract Oncol 3:138-51
Barsky, Sanford H; Karlin, Nina J (2005) Myoepithelial cells: autocrine and paracrine suppressors of breast cancer progression. J Mammary Gland Biol Neoplasia 10:249-60
Barsky, Sanford H (2003) Myoepithelial mRNA expression profiling reveals a common tumor-suppressor phenotype. Exp Mol Pathol 74:113-22
Shao, Z M; Nguyen, M; Barsky, S H (2000) Human breast carcinoma desmoplasia is PDGF initiated. Oncogene 19:4337-45
Shao, Z M; Shen, Z Z; Fontana, J A et al. (2000) Genistein's ""ER-dependent and independent"" actions are mediated through ER pathways in ER-positive breast carcinoma cell lines. Anticancer Res 20:2409-16
Shao, Z M; Alpaugh, M L; Fontana, J A et al. (1998) Genistein inhibits proliferation similarly in estrogen receptor-positive and negative human breast carcinoma cell lines characterized by P21WAF1/CIP1 induction, G2/M arrest, and apoptosis. J Cell Biochem 69:44-54
Shao, Z M; Wu, J; Shen, Z Z et al. (1998) Genistein inhibits both constitutive and EGF-stimulated invasion in ER-negative human breast carcinoma cell lines. Anticancer Res 18:1435-9
Shao, Z M; Nguyen, M; Alpaugh, M L et al. (1998) The human myoepithelial cell exerts antiproliferative effects on breast carcinoma cells characterized by p21WAF1/CIP1 induction, G2/M arrest, and apoptosis. Exp Cell Res 241:394-403
Shao, Z M; Wu, J; Shen, Z Z et al. (1998) Genistein exerts multiple suppressive effects on human breast carcinoma cells. Cancer Res 58:4851-7

Showing the most recent 10 out of 38 publications