Submission Number: NEL-4-329-155

Abstract Number: 1

E-CADHERIN/HEPATOCYTE GROWTH FACTOR INTERACTIONS IN OVARIAN CARCINOGENESIS.

Nelly Auersperg*, Alice ST Wong and Peter CK Leung

University of British Columbia, Vancouver, BC, Canada ¹

Abstract:
The ovarian surface epithelium (OSE), which gives rise to epithelial ovarian carcinomas, is derived from the coelomic epithelium that overlies the developing gonads and also gives rise to the epithelia of the oviduct and endometrium. Adult OSE, which lacks E-cadherin, retains the competence to differentiate along these pathways because, during neoplastic progression, it acquires complex structural and functional characteristics of the oviductal and endometrial epithelia. These characteristics include hepatocyte growth factor (HGF) secretion and autocrine regulation of the HGF receptor Met, the expression of E-cadherin, and the formation of glands and papillae. HGF and E-cadherin interact in gland formation and tubular morphogenesis in other systems. To determine whether Met activation and E-cadherin expression contribute to the aberrant differentiation of neoplastic OSE, we examined collagen gel cultures of different forms of human OSE in the presence and absence of HGF and E-cadherin. Control cells and cells treated with HGF alone dispersed and became stationary. Tumorigenic OSE cells constitutively expressing transfected E-cadherin formed round aggregates and cystic structures. Cells expressing E-cadherin and stimulated by HGF underwent branching morphogenesis and tubulogenesis. When overtly normal low passage OSE cultures from women with family histories of ovarian cancer (FH-OSE) were compared to cultures from women without such histories (NFH-OSE), FH-OSE cultures expressed HGF and E-cadherin at significantly higher frequencies than NFH-OSE. These results suggest that HGF/E-cadherin interactions may contribute to the aberrant differentiation of neoplastic OSE, and this trend may be an early or predisposing factor in ovarian carcinogenesis. Supported by NCIC Canada.

Keywords: ovary, cancer, E-cadherin, hepatocyte growth factor

This abstract is being presented at: 10:30 AM in session:
Minisymposium XIV: CELLULAR AND MOLECULAR BASIS OF HUMAN OVARIAN CANCER: FROM BENCH TO BEDSIDE