Expression of the macrophage colony-stimulating factor and its receptor in gynecologic malignancies.
Recently, hematopoietic growth factors have been implicated in protean nonhematopoietic processes. In the current study, expression of macrophage colony-stimulating factor (M-CSF) and its receptor (the c-fms proto-oncogene) was investigated in 42 samples of gynecologic tissues. There were 15 samples of normal ovarian and uterine tissue or benign conditions of these organs; 11 samples of primary ovarian cancer tissue; seven samples of metastatic ovarian cancer tissue; and nine samples of primary endometrial cancer tissue. Steady state transcript levels were assessed by Northern Blot analysis. Macrophage colony-stimulating factor (M-CSF) expression was not observed in any of the specimens of benign abnormalities or of normal organs; c-fms expression was detected in two of 15 (13%) of these specimens, albeit at very low levels. In contrast, 14 (78%) of 18 ovarian tumor specimens, and five (55%) of nine endometrial tumor specimens expressed M-CSF. Similarly, 16 (89%) of 18 ovarian tumor specimens and six (67%) of nine endometrial tumor specimens expressed c-fms. Most positive malignant tissues (19 [86%] of 22) showed coexpression of M-CSF and c-fms. Of interest, M-CSF and c-fms mRNA were detected in tumor, but not in adjacent normal tissue. Furthermore, M-CSF and c-fms transcripts were produced by all metastatic tumors, including two cases in which the corresponding primary tumor from the same patient was negative. Because M-CSF mediates its effects by binding to its receptor, the increased levels of both these gene products in gynecologic malignancies suggest that an interaction between M-CSF and c-fms may participate in the development of ovarian and endometrial carcinomas and especially in progression to the metastatic state.
Baiocchi
G
G
Department of Clinical Immunology, University of Texas, M. D. Anderson Cancer Center, Houston 77030.
Kavanagh
J J
JJ
Talpaz
M
M
Wharton
J T
JT
Gutterman
J U
JU
Kurzrock
R
R
D015152:Blotting, Northern; D005260:Female; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis* / Q000235:genetics; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D010053:Ovary / Q000737:chemistry; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis; D012016:Reference Values; D014594:Uterine Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D014599:Uterus / Q000737:chemistry
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor