Accession Number : ADA302414

Title :   Studies on Platelet-Derived Growth Factor Beta-Receptor and Hepatocyte Growth Factor Receptor c-met in Paracrine Interactions in Human Breast Cancer.

Descriptive Note : Annual rept. 1 Sep 94-31 Aug 95,

Corporate Author : QUEEN'S UNIV KINGSTON (ONTARIO)

Personal Author(s) : Elliot, Bruce E.

PDF Url : ADA302414

Report Date : SEP 1995

Pagination or Media Count : 111

Abstract : Platelet-derived growth factor (pDGF) and hepatocyte growth factor (HGF) are key regulators of breast stromal- epithelial interactions. We examined the expression of PDGF 13-receptor, HGF receptor/Met and the corresponding ligands in primary human breast cancer using in situ hybridization and imunohistochemical techniques. The results showed that PDGF 13-receptor was localized in smooth musclie-actin-positive cells and vascular endothelial cells in the periepithelial stroma, but not in the epithelial component of ductal carcinoma in situ. These findings support the notion that PDGF BB, which is produced by breast carcinoma cells, functions in the paracrine stimulation of the stroma by adjacent carcinoma cells. In contrast, HGF receptor/Met was exclusively expressed on nonmalignant and malignant epithelial cells. However, HGF mRNA was expressed in both stromal cells and in carcinoma cells in regions of invasive cancer; these results. suggest that both paracrine and autocrine stimulation by HGF of mammary carcinoma cells can occur. Our hypothesis is that co-expression of HGF and HGF receptor/Met results in the establishment of an HGF autocrine loop which provides a selective advantage for autonomous growth and metastasis of mammary carcinoma cells. To further investigate the possible role of an HGF autocrine loop in the progression of breast cancer, we are currently examining expression and function of HGF in human and murine primary breast carcinomas and carcinoma cell lines.

Descriptors :   *CELLS(BIOLOGY), *MAMMARY GLANDS, *GROWTH(PHYSIOLOGY), *BLOOD PLATELETS, *METASTASIS, *BREAST CANCER, EPITHELIUM, STIMULATION(GENERAL), HUMANS, INTERACTIONS, NEOPLASMS, REGIONS, REGULATORS, LIGANDS, SELF OPERATION, HYPOTHESES, LIVER, CARDIOVASCULAR SYSTEM, CANCER, ENDOTHELIUM, HYBRIDIZATION.

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE