CSF-1 and Its Receptor in Ovarian, Endometrial and Breast Cancer

Abstract

The aim of this report is to review the role of CSF-1 and its receptor in neoplasms of the breast and female reproductive tract. Expression and function of CSF-1 and its receptor were studied in tumours 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, ovary and endometrium where activation of the receptor by ligand produced either by the tumour cells or by stromal elements stimulates tumour cell invasion by a urokinase-dependent mechanism. Breast carcinomas express wild-type CSF-1 receptors at levels comparable to those observed in trophoblast and monocytes. Ovarian and endometrial carcinomas express significantly lower levels of wild-type, functional CSF-1 Rs while ovarian carcinomas also express unusual transcripts which diverge from the wild-type CSF-1 R transcript in their 5′ extracellular and other sequences. Tumour cell expression of CSF-1 R is under the control of several steroid hormones (glucocorticoids and progestins) and tumour cell CSF-1 expression appears to be regulated by other hormones, some of which are Involved in normal lactogenic differentiation. In addition, tumour cells often produce CSF-1 at such high levels that CSF-1 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 patients 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 tumours of the female reproductive tract where they may regulate functions similar to those which they control during macrophage activation and placental implantation.