The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma

Department of Obstetrics and Gynecology, Department of Developmental and Molecular Biology, and Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York 10461, USA.
Clinical Cancer Research (Impact Factor: 8.72). 04/1995; 1(3):313-25.
Source: PubMed


Colony-stimulating factor 1 (CSF-1) is a homodimeric growth factor that humorally regulates the growth and differentiation of mononuclear phagocytes, and locally regulates maternal-fetal interactions during pregnancy. It exerts these actions through a transmembrane tyrosine kinase receptor, colony-stimulating factor 1 receptor (CSF-1R), the product of the c-fms proto-oncogene. Recent studies have demonstrated overexpression of CSF-1 and its receptor in breast, ovarian, and endometrial adenocarcinomas. To further investigate the possible role of CSF-1 and its receptor in the pathogenesis of endometrial adenocarcinoma, a prospective study was undertaken to study CSF-1 expression in benign and neoplastic endometrial epithelium and to compare serum CSF-1 levels in endometrial adenocarcinoma patients with healthy perimenopausal women. The mean serum levels of CSF-1 in 71 patients with endometrial cancer (4.9 +/- 1.8 microgram/liter) were significantly elevated compared with levels found in the 32 controls (3.5 +/- 1.1 microgram/liter). Within the endometrial adenocarcinoma group, circulating CSF-1 levels were significantly elevated in patients with large tumor volume, high grade, myometrial invasion, residual disease, and circulating CA-125 levels. High serum levels of serum CSF-1 were associated with elevated serum CA19-9 and CA-125 levels. Immunohistochemistry results revealed in tumor epithelium intense staining for CSF-1R (27 of 54 cases, 50%) and elevated staining for CSF-1 (41 of 54 cases, 75.9%), with intense staining of CSF-1 in 16 of 54 cases (29.6%). Staining was significantly greater in intensity and number of cells involved in malignant compared with benign epithelium for CSF-1R and CSF-1 (P = 0.05 and <0.0001, respectively). A positive correlation between amount and intensity of CSF-1 and CSF-1R staining in endometrial adenocarcinoma tissue was also demonstrated (P = 0.007). CSF-1 and CSF-1R mRNA was also detected in the tumor samples, confirming the expression of the protein in these tissues. Reverse transcription-PCR demonstrated the presence of mRNA for both the transmembrane and secreted forms of CSF-1 in all tumors analyzed. These results therefore support the hypotheses that CSF-1 and CSF-1R are overexpressed in endometrial adenocarcinoma, that levels of expression significantly correlate with clinicopathological risk factors for poor outcome, and that CSF-1 in association with its receptor via autocrine, juxtacrine, and/or paracrine interactions has a causal role in endometrial adenocarcinoma development and proliferation.

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    • "The tumor microenvironment with abundance of tumor associated macrophages density often has a correlation with poor prognosis [4]. The TAMs recruit chemokine and CSF-1 in excess which is proportional to the prognosis [38, 39]. More than about 80% of tumors have shown a positive correlation between the poor prognosis and TAMs, then only tumors less than 10% of TAMs density demonstrated good prognosis [4]. "
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    • "MCSF was known to be a pro-tumoral cytokine. The elevated expression of MCSF along with its receptor CSF1R in breast, uterine and ovarian cancer was associated with tumor progression [31], [32]. Further, high level of MCSF in several tumors had been strongly associated with poor prognosis [33], [34].Our results provide evidence for MCSF increasing the resistance of tumor cells to 5-FU, by upregulating the expression of MDR associated genes. "
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