Differential responsiveness of murine T lymphomas to local growth and invasion factors may determine metastasis formation in the ovaries.

Abstract

The murine T cell hybridomas BW-14 and BW-19, both derived from a fusion between the nonmetastatic BW 5147 lymphoma and a cytotoxic T cell line, differ in their capacity to metastasize to the ovaries. While ovary colonization by BW-19 cells is marginal and limited to the ovary follicles, BW-14 cells extensively colonize the complete ovary. The present study shows that the two T cell hybridomas respond differentially to ovary-derived migration and growth-modulating factors, in a way that correlates with their differential capacity to metastasize to the ovaries. More specifically, we observed that conditioned medium from cultured ovary fragments or from the ovary-derived granulosa cell line GRMO1V inhibited the migration of BW-19 cells in vitro, but stimulated the migration of BW-14 cells. Likewise, the local hormone prostaglandin E2 (PGE2) and the steroid hormone progesterone, both known to be secreted by GRMO1V cells, stimulated the migration of BW-14 cells, indicating that the stimulatory effect of the conditioned medium can be at least partially ascribed to the action of these two hormones. In contrast, the migration of BW-19 cells was inhibited by PGE2. In addition to the modulatory effect on hybridoma cell migration, conditioned medium from the granulosa cell line GRMO1V inhibited the proliferation of BW-19 cells in vitro, an effect that is likely to be mediated at least partially by PGE2. The proliferation of BW-14 cells, on the other hand was, depending on the dilution used, stimulated or inhibited by GRMO1V-conditioned medium. Our findings indicate that the differential capacity of the T cell hybridomas BW-14 and BW-19 to metastasize to the ovaries is mediated by the differential action of granulosa-cell-derived factors, in particular the sex hormone progesterone and the local hormone PGE2, on both the migration and proliferation of the T cell hybridomas.