RECIPROCAL INTERACTIONS BETWEEN HUMAN OVARIAN SURFACE EPITHELIAL-CELLS AND ADJACENT EXTRACELLULAR-MATRIX

The human ovarian surface epithelium (OSE), or ovarian mesothelium, is functionally complex as seen by its capacity to proliferate, migrate, and contribute to ovulation and ovulatory repair in response to cycli c hormonal and environmental changes. We wished to determine whether t his phenotypic versatility is reflected in cell-extracellular matrix i nteractions in primary and low-passage culture. Comparisons of culture s maintained on different substrata revealed that these cells form coh esive monolayers on plastic, while fibrin clots enhance cell dispersio n, and thus may provide a migratory cue. The cells invaded Matrigel as multicellular aggregates, while collagen gels mediated a morphologic epithelial-mesenchymal conversion. On plastic, the cells produced extr acellular matrix components characteristic of epithelial basement memb rane (laminin and collagen type IV), as well as stroma (collagen types I and III). In addition, ovarian surface epithelial cells secreted se rine proteases and matrix metalloproteinases. The levels of chymotryps in- and elastase-like proteases were dictated by the substratum: low l evels were secreted by cells grown on plastic, intermediate levels on collagen gels and fibrin clots, and most protease was produced on Matr igel. The rate of cell proliferation varied with the substrata and was inversely related to protease secretion. Integrin expression was grea test on plastic and least on collagen gels where integrins were downre gulated with time. (alpha 6/beta 4 was absent from all cells while var ying levels of alpha 2, alpha 3, alpha 5, beta 1, and vitronectin rece ptor were detected depending on the culture substratum employed. In lo w-passage cultures of human ovarian surface epithelial cells, then, ce ll shape, growth, protease production, and integrin expression are mod ulated by the extracellular matrix. The cells, in turn, alter extracel lular matrix by synthesis, lysis, and physical remodeling, and express both stromal and epithelial characteristics. The broad repertoire of these functions may be related to their mesodermal origin, and may ref lect the expression of a dual, epithelio-mesenchymal phenotype by rela tively immature, uncommitted cells. The results demonstrate the great complexity and versatility of these interactions which render OSE cell s capable of participating in numerous physiological and pathological processes. (c) 1994 Academic Press, Inc.