Transforming growth factor-β regulates Kit ligand expression in rat ovarian surface epithelial cells

Abstract

In preparation for ovulation, paracrine communication between the preovulatory follicle and overlying theca/ stromal cells and ovarian surface epithelium (OSE) must take place to facilitate the degradative and apoptotic events associated with ovulation. Kit tyrosine kinase receptors and their ligand, kit ligand (KL) are expressed within ovarian follicles, and ligand-induced receptor activation appears to account for some of the cell ± cell interactions important for oocyte development. We investigated the expression of Kit receptors and KL in OSE cells and the possibility that modulation of their expression could a ect OSE cell activity. KL mRNA and protein were detected in the OSE cell layer of rat ovaries, and primary cultures of rat OSE as well as the immortalized rat OSE cell line, ROSE 199, expressed KL, but not Kit receptors. Both primary and immortalized OSE cells preferentially expressed KL-1, rather than KL-2, transcripts, suggesting that these cells produce predominantly the soluble form of KL. Activation of the cAMP signalling pathway using dibutyryl cAMP decreased proliferation of ROSE 199 cells and elicited a threefold increase in KL expression. TGF-b similarly inhibited ROSE 199 cell proliferation, but strongly inhibited dibutyryl cAMP-induced KL expression, indicating that changes in KL expression were not directly associated with OSE cell proliferation. The expression of mostly soluble KL in the surface epithelium suggests that this cytokine may be acting in a paracrine fashion, perhaps interacting with nearby Kit receptorbearing theca cells.

Expression and Action of Transforming Growth Factor Alpha in Normal Ovarian Surface Epithelium and Ovarian Cancer1

“…Transforming growth factor beta was used as a positive control and found to stimulate KGF and KL gene expression. This is in contrast to a previous observation that demonstrated that TGF␤ can inhibit the ability of cAMP to stimulate KL gene expression [55]. Whether differences in assay sensitivity or basal levels of gene expression is the reason for differences between this and the current study remains to be investigated.…”

Aberrant Mucosal Mast Cell Protease Expression in the Enteric Epithelium of Nematode-Infected Mice Lacking the Integrin αvβ6, a Transforming Growth Factor-β1 Activator

“…This may be an additional outcome of decreased epithelial levels of active TGF-␤ 1 ; TGF-␤ 1 has been shown to inhibit SCF production by ovarian epithelial cells. 61 In wild-type mice, levels of epithelial SCF transcripts did not change on infection, in agreement with previous findings in mice infected with Nippostrongylus brasiliensis. 39 SCF is a key regulator of T. spiralisinduced intestinal mastocytosis, 37,38 SCF is produced by the small intestinal epithelium 39 and has both systemic and local effects on mast cell development.…”

“…64 Preferential expression of KL-1 rather than KL-2 can be associated with increased production of the soluble form of SCF in epithelial cells. 61,64 Here, we have found that the KL-1 splice variant of SCF is preferentially expressed in infected ␤ 6 Ϫ/Ϫ mice in relation to KL-2, possibly favoring local production of SCF that can be more readily cleaved to its soluble form. Local up-regulation of SCF, diffusing from the epithelium, may contribute to increased proliferation of MMCs in the lamina propria of ␤ 6 Ϫ/Ϫ mice.…”

CD117 Expression in Fibroblasts-Like Stromal Cells Indicates Unfavorable Clinical Outcomes in Ovarian Carcinoma Patients

“…CD117 is mostly reported in mast cells/myeloid cells (mastocytoma/acute myeloid leukemia) [18], germ cells (seminoma) [19], Cajal cell (gastrointestinal stromal tumors) [20], [21] and some epithelial cells [22], [23], [24], [25]. CD117 expression in tumor stromal cells is neglected and rarely reported.…”