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AGENCY USE ONLY (Leave blank)2. REPORT DATE December 1999
REPORT TYPE AND DATES COVEREDFinal (1 Dec 94 -30 Nov 99)
TITLE AND SUBTITLE
Role of Tumor Collagenase Stimulating Factor in BreastCancer Invasion and Metastasis 6. AUTHOR(S) Stanley Zucker, M.
PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)The
SUPPLEMENTARY NOTES
12a. DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release; distribution unlimited 12b. DISTRIBUTION CODE
ABSTRACT (Maximum 200Extracellular matrix metalloproteinase inhibitor {EMMPRIN), a plasma membrane glycoprotein identified originally in carcinoma cells, is responsible for inducing peritumoral fibroblasts to produce matrix metalloproteinases (MMPs), thereby enhancing cancer invasion and metastasis. Using in situ hybridization and immunohistochemistry, we have identified EMMPRIN in breast cancer tissue. We have characterized the human EMMPRIN gene and have noted a high degree of conservation with the mouse gene. The effect of transfecting human breast cancer cells with EMMPRIN cDNA was explored. Expression of EMMPRIN cDNA by MDA-MB-436 cancer cells resulted in marked increase in tumor growth and invasiveness after tumor cell injection into mammary tissue of nude mice. Using the phage display system, crosslinking and ligand affinity chromatography, MMP-1 binding to EMMPRIN was identified suggesting the novel possibility that EMMPRIN binds MMP-1 to the tumor cell surface, thus enhancing pericellular degradation of extracellular matrix. The effect of EMMPRIN on endothelial MMPs was explored in vitro; EMMPRIN enhanced endothelial production of stromelysin-1, collagenase, and gelatinase A. These data support a role for EMMPRIN in enhancing cancer dissemination. Where copyrighted material is quoted, permission has been obtained to use such material.
SUBJECT TERMSWhere material from documents designated for limited distribution is quoted, permission has been obtained to use the material. The purpose of this grant has been to determine the role of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) in breast cancer invasion and metastasis. EMMPRIN is a glycoprotein identified on the plasma membrane of cancer cells which induces fibroblasts to produce Matrix Metalloproteinases (MMPs) (l).Originally known as Tumor Collagenase Stimulating Factor (TCSF) because it was described as a stimulator of inter...