| Summary: | The ovarian surface epithelium (OSE) is thought to give rise to 85% of ovarian
cancers, predominantly in invaginating clefts and cysts in the ovarian stroma. The cells of
the ovarian neoplasms express more complex epithelial characteristics than the cuboidal
OSE on the surface. As well, ovarian cancer cells when cultured retain their epithelial
characteristics whereas OSE expresses a dual epithelial-mesenchymal phenotype and
gradually loses its epithelial characteristics. These observations raised several questions: 1)
could cyst-like structures be developed in culture; 2) could improving culture conditions
avoid the loss of epithelial characteristics by OSE; and 3) were variations in expression of
epithelial and mesenchymal characteristics clinically significant.
This study used a rat OSE line (ROSE 199) to explore the use of two collagenous 3-D
culture systems for the development of cysts: seeding cells in sponges and gels. The
impact of collagen on the morphology of these cells was also assessed using collagen coats
and seeding on gels. It became apparent that two sublines of ROSE 199 had developed
that differed in the amount of matrix deposited and in the ability to migrate into the
extracellular matrix (ECM); one subline exhibiting a predominantly epithelial response
whereas the other showed characteristics of an epithelial-mesenchymal conversion
response. The collagen sponge supported the formation of cyst-like structures and affected
the organization, but not the types, of basic E CM components produced by the ROSE 199
High ECM subline. Therefore the sponge system is useful for developing cyst and cleftlike
structures in culture, while the two sublines may be useful for determining the signals
that trigger the mesenchymal response in OSE.
Co-culturing ROSE 199 with human OSE was used in an attempt to improve culture
conditions that would maintain the original characteristics of the latter. ROSE 199, like
human OSE in culture, produces both epithelial and mesenchymal E CM components.
However, unlike human OSE, it forms a cuboidal epithelium on a thick autologous matrix
with underlying cellular layers. It was hoped that ROSE 199 could provide the signals that
human OSE needed to maintain their epithelial characteristics. This did not occur. Instead,
the human OSE cells migrated into the ROSE matrix assuming a mesenchymal
morphology even when able to maintain epithelial colonies when grown alone. Therefore
this system does not improve the retention of epithelial characteristics by human OSE.
Thirdly, the study examined whether neoplastic progression or genetic changes
associated with a family history of ovarian cancer affected the expression of epithelial and
mesenchymal characteristics. Normal OSE from women with (FH-OSE) and without
(NFH-OSE) a family history of ovarian cancer, SV40 immortalized lines of each, and
ovarian cancer lines were compared. The parameters examined were keratin and collagen
III expression as cytodifferentiation markers, and three-dimensional morphogenesis. The
results indicate there is a decrease in expression of mesenchymal characteristics with
neoplastic progression while epithelial characteristics are maintained, and that FH-OSE
cells are phenotypically different from NFH-OSE and are less prone to undergo epithelialmesenchymal
conversion in culture. This suggests that an increase in commitment to an
epithelial phenotype and/or reduced responsiveness to signals in culture may be one of the
earliest changes in the process of ovarian carcinogenesis. === Medicine, Faculty of === Graduate
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