Expression and hormonal regulation of monocyte chemotactic protein-1 in myometrium and leiomyomata

Abstract

Objective: The pathogenesis of leiomyoma likely involves interactions of sex steroids with paracrine growth factors or cytokines resulting in modulation of local immunity. Monocyte chemotactic protein-1 (MCP-1) is a chemotactic and activating factor for monocytes and is produced by multiple tumors and has antitumor effects. We investigated the expression of MCP-1 in leiomyoma and myometrium as well as the regulatory role of steroid hormones and cytokines on MCP-1 expression and the effect of MCP-1 on the proliferation of leiomyoma cells. Design: Prospective study. Setting: University medical center. Patient(s): Women with (n = 20) or without (n = 11) leiomyoma. Intervention(s): First, MCP-1 messenger RNA (mRNA) levels in myometrium and leiomyoma were measured, and then myometrial and leiomyoma cells in culture were treated with steroid hormones and cytokines. Main Outcome Measure(s): The MCP-1 mRNA was evaluated by Northern analysis. Immunoreactive MCP-1 in cell cultures was quantified by ELISA. Leiomyoma cell proliferation was assessed with [3H]thymidine incorporation. Result(s): The MCP-1 mRNA levels in myometrial samples were 4.7-fold higher than in the leiomyoma samples. Myometrial MCP-1 mRNA levels were 2.4-fold higher in secretory than in proliferative phase samples. The highest MCP-1 levels were observed in samples from women using GnRH analogues. Estradiol and progestins, alone or in combination, resulted in a decrease in MCP-1 protein production. There was an increase in the proliferation of leiomyoma cells treated with anti-MCP-1 neutralizing antibody. Conclusion(s): These findings suggest that MCP-1 may have antineoplastic activity in leiomyomata and that sex steroids may be exerting their growth stimulatory effect in leiomyomata through down-regulation of MCP-1.