CSF-1 and its receptor in breast carcinomas and neoplasms of the female reproductive tract

Abstract

The expression and function of CSF-1 and its receptor were studied in tumors of the human breast, ovary, and endometrium. CSF-1 and its receptor, initially implicated as essential to normal monocyte development and trophoblastic implantation, have been more recently shown to be expressed by carcinomas of the breast and other epithelia of the female reproductive tract where activation of the receptor by ligand produced either by the tumor cells or by stromal elements stimulates tumor cell invasion by a urokinase-dependent mechanism. Breast carcinomas express wild-type CSF-1 receptors (CSF-1R) at levels comparable to those observed in trophoblast and monocytes. Ovarian and endometrial carcinomas express significantly lower levels of wild-type, functional CSF-1Rs, while ovarian carcinomas also express unusual transcripts that diverge from the wild-type CSF-1R transcript in their 5' extracellular domain sequences. Tumor cell expression of CSF-1R is under the control of several steroid hormones (glucocorticoids and progestins) and the binding of several bHLH transcription factors, while tumor cell expression of CSF-1 appears to be regulated by other hormones, some of which are involved in normal lactogenic differentiation. In addition, tumor cells often produce CSF-1 at such high levels that the cytokine spills into the extracellular fluid and circulation. Measurements of circulating levels of CSF-1 have proved useful in patients with ovarian, endometrial, and breast carcinoma both for disease detection and monitoring of response to therapy. CSF-1 and its receptor appear to be an important receptor/ligand pair in the biology of breast cancers and tumors of the female reproductive tract where they may regulate functions similar to those they control during macrophage activation and placental implantation.