Menstrual cycle-specific inhibition of endometrial stromal cell proliferation by oncostatin M

Abstract

We have investigated the possible roles of oncostatin M (OSM), which is a member of the interleukin-6 family of cytokines, in endometrial and endometriotic stromal cell growth. Endometrial and endometriotic stromal cells were collected from the uterus or ovarian chocolate cysts. We observed the expression of mRNA transcripts for OSM, OSM receptor subunit beta, leukaemia inhibitory factor receptor subunit (LIFR), and glycoprotein 130 in endometrial and endometriotic stromal cells. We also examined the effects of OSM (0-50 ng/ml) and LIF (0-10 ng/ml) on endometrial and endometriotic stromal cell proliferation and evaluated the effects of OSM on endometrial stromal cell differentiation. The presence of 10-50 ng/ml OSM significantly suppressed endometrial stromal cell growth in secretory phase tissue but not in proliferative phase tissue. In contrast, stromal cells in endometriotic tissues were resistant to the inhibitory effects of OSM. Addition of LIF did not influence the growth of endometrial stromal cells. We also showed that 10 ng/ml OSM stimulated markers of differentiation causing increased prolactin secretion and cyclooxygenase-2 gene expression in endometrial stromal cells from the secretory phase. These results suggest that OSM may play a pivotal role in regulating the growth and differentiation of endometrial cells. Endometriotic cells may behave differently from normal endometrial cells in terms of the inhibitory response to OSM.

Promoter DNA Methylation of Oncostatin M receptor-β as a Novel Diagnostic and Therapeutic Marker in Colon Cancer

“…Human OSM was originally described by its capacity to inhibit melanoma proliferation in vitro [33], [34], and its targets for growth inhibition include lung carcinomas [35], ovarian carcinomas [36], and breast tumors [37]. Resistance to growth inhibition by OSM in metastatic melanoma cell lines correlated with a specific loss of OSMR, in conjunction with a lower level of histone acetylation in the OSMR promoter region, suggesting that metastatic melanoma cells could escape the growth control of OSM by the epigenetic silencing of OSMR [15].…”

Leukaemia inhibitory factor in implantation and uterine biology

“…4). The role of OsM has not been previously investigated in the mouse uterus, but the in human it is reported to reduce proliferation and induce differentiation in uterine stroma in the secretory phase (Ogata et al 2000, Ohata et al 2001) and has been implicated in tissue remodelling in other systems. It has been shown to upregulate both matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in diverse cell types (Richards et al 1993, Korzus et al 1997, Sanchez et al 2004 as well as tissue plasminogen activator and plasminogen activator inhibitor (Macfelda et al 2002, Spence et al 2002, while in human vascular smooth muscle cells it induces alkaline phosphatase (Shioi et al 2002) and in astocytes Cox-2 (Repovic et al 2003).…”

Oncostatin M (OSM) Cytostasis of Breast Tumor Cells: Characterization of an OSM Receptor β–Specific Kernel

“…Targets for human OSM-mediated growth inhibition include melanoma (3,4), glioblastoma (12), lung carcinomas (13), ovarian carcinomas (14), and breast tumors (15,16). In addition, human OSM induces differentiation of several tumor cell types (12,17).…”