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-1Rs while ovarian carcinomas also express unusual transcripts which diverge from the wild-type CSF-1R transcript in their 5' extracellular and other sequences. Tumour cell expression of CSF-1R 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 breast carcinoma patients both for disease detection and monitoring of response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis and breakdown of fibrillar collagens: concomitant phenomena in ovarian cancer

“…We have confirmed here that CSF-I concentration in ascitic fluid is increased in patients with ovarian carcinoma (Kacinski, 1992(Kacinski, , 1995Price et al, 1993). The present median concentration of CSF-I in ascites was the same as in the study of Price et al (1993).…”

“…CSF-1 might be causally linked to enhanced collagen metabolism in ovarian cancer (Jennings et al, 1994), as we had supposed to be the case for endometrial cancer (Hakala et al, 1995 (Kacinski, 1992(Kacinski, , 1995, which are known to stimulate collagen production in the fibroblastic cells (Sporn and Roberts, 1992 (Kacinski, 1995), and that ovarian and endometrial cancer behave differently in this respect, may explain the conflicting finding.…”

“…CSF-1 has an important role in the regulation of the neoplastic disease activity of ovarian cancer (Kacinski, 1992(Kacinski, , 1995, and it has potential to be a practical tumour marker in patients with gynaecological (Kacinski et al, 1989(Kacinski et al, , 1990Hakala et al, 1995) and other malignant diseases (Janowska-Wieczorek et al, 1991). We have confirmed here that CSF-I concentration in ascitic fluid is increased in patients with ovarian carcinoma (Kacinski, 1992(Kacinski, , 1995Price et al, 1993).…”

“…The cytokine macrophage colony-stimulating factor 1 (CSF-1) stimulates the proliferation and differentiation of monocytes, is a chemoattractant for macrophages and may be involved in the pathogenesis of ovarian and some other malignancies (Kacinski, 1995). Neoplastic epithelial cells synthesize CSF-1 and increase CSF-l production through macrophage activation, which in turn may stimulate further growth of the neoplasm, particularly when the tumour cells themselves express receptors for this cytokine (Kacinski, 1995). Further support for this approach comes from observations that macrophage-conditioned media enhance stromal cell proliferation (Olive et al, 1991).…”

Modulation of c-fms proto-oncogene in an ovarian carcinoma cell line by a hammerhead ribozyme

“…To date, a predominant number of breast, ovarian and endometrial carcinomas are known to express the cfins gene (Kacinski et al, 1990;Kacinski et al, 1991;. The expression level of c-fins transcripts in ovarian epithelial carcinoma has been described as correlating strongly with high-grade histology, advanced clinical presentations and poor outcome of the patients (Kacinski, 1995).…”