Our long-term goal is to understand the function of the basal lamina, a component of the basement membrane, in cellulose physiology and in various pathological states. Our studies have shown that mouse mammary epithelial cells cultured on a collagen gel substratum form a proteoglycan-containing basal lamina. Basal lamina formation correlates with reduced glycosaminoglycan degradation and the apparent conversion of a cellular proteoglycan fraction to a slowly degrading extracellular fraction. Similarly cultured neoplastically transformed cells of the same origin show defective lamina formation and lack of proteoglycan processing. Based upon the hypothesis that the presence and interactions of the proteoglycans in the basal lamina are crucial to its structure and function, we will continue these studies. Using mouse mammary epithelial cells in culture, the focus will be on: (1) isolating and purifying the various proteoglycans and determining the structural relationships between them by analyzing their protein and glycosaminglycan components; (2) elucidating the macromolecular organization of the proteoglycan-containing basal lamina by analyzing the interactions of its various extracellular matrix constituents; (3) establishing the steps in the processing and degradation of basal laminar proteoglycans to determine the role of the collagen substratum in facilitating lamina formation; and (4) applying this new information to elucidate the basis for the defective lamina formation shown by the malignant cells. The functional role of proteoglycans in the lamina will be further assessed by comparing laminar proteoglycans of cultured mammary and vascular endothelial cells.

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National Cancer Institute (NCI)
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Pathobiochemistry Study Section (PBC)
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Stanford University
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Long, Olivia S; Gosai, Sager J; Kwak, Joon Hyeok et al. (2011) Using Caenorhabditis elegans to study serpinopathies. Methods Enzymol 499:259-81
Reizes, Ofer; Goldberger, Olga; Smith, April C et al. (2006) Insulin promotes shedding of syndecan ectodomains from 3T3-L1 adipocytes: a proposed mechanism for stabilization of extracellular lipoprotein lipase. Biochemistry 45:5703-11
Gotte, Martin; Bernfield, Merton; Joussen, Antonia M (2005) Increased leukocyte-endothelial interactions in syndecan-1-deficient mice involve heparan sulfate-dependent and -independent steps. Curr Eye Res 30:417-22
Wang, Zihua; Gotte, Martin; Bernfield, Merton et al. (2005) Constitutive and accelerated shedding of murine syndecan-1 is mediated by cleavage of its core protein at a specific juxtamembrane site. Biochemistry 44:12355-61
Elenius, Varpu; Gotte, Martin; Reizes, Ofer et al. (2004) Inhibition by the soluble syndecan-1 ectodomains delays wound repair in mice overexpressing syndecan-1. J Biol Chem 279:41928-35
Gotte, Martin (2003) Syndecans in inflammation. FASEB J 17:575-91
Gotte, Martin; Joussen, Antonia M; Klein, Christoph et al. (2002) Role of syndecan-1 in leukocyte-endothelial interactions in the ocular vasculature. Invest Ophthalmol Vis Sci 43:1135-41
Park, P W; Pier, G B; Preston, M J et al. (2000) Syndecan-1 shedding is enhanced by LasA, a secreted virulence factor of Pseudomonas aeruginosa. J Biol Chem 275:3057-64
Fitzgerald, M L; Wang, Z; Park, P W et al. (2000) Shedding of syndecan-1 and -4 ectodomains is regulated by multiple signaling pathways and mediated by a TIMP-3-sensitive metalloproteinase. J Cell Biol 148:811-24
Park, P W; Reizes, O; Bernfield, M (2000) Cell surface heparan sulfate proteoglycans: selective regulators of ligand-receptor encounters. J Biol Chem 275:29923-6

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