The detection and localization of monocyte chemoattractant protein-1 (MCP-1) in human ovarian cancer.
Chemokines may control the macrophage infiltrate found in many solid tumors. In human ovarian cancer, in situ hybridization detected mRNA for the macrophage chemokine monocyte chemoattractant protein-1 (MCP-1) in 16/17 serous carcinomas, 4/4 mucinous carcinomas, 2/2 endometrioid carcinomas, and 1/3 borderline tumors. In serous tumors, mRNA expression mainly localized to the epithelial areas, as did immunoreactive MCP-1 protein. In the other tumors, both stromal and epithelial expression were seen. All tumors contained variable numbers of cells positive for the macrophage marker CD68. MCP-1 mRNA was also detected in the stroma of 5/5 normal ovaries. RT-PCR demonstrated mRNA for MCP-1 in 7/7 serous carcinomas and 6/6 ovarian cancer cell lines. MCP-1 protein was detected by ELISA in ascites from patients with ovarian cancer (mean 4.28 ng/ml) and was produced primarily by the cancer cells. Human MCP-1 protein was also detected in culture supernatants from cell lines and in ascites from human ovarian tumor xenografts which induce a peritoneal monocytosis in nude mice. We conclude that the macrophage chemoattractant MCP-1 is produced by epithelial ovarian cancer and that the tumor cells themselves are probably a major source. MCP-1 may contribute to the accumulation of tumor-associated macrophages, which may subsequently influence tumor behavior.
Negus
R P
RP
Biological Therapies Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
Stamp
G W
GW
Relf
M G
MG
Burke
F
F
Malik
S T
ST
Bernasconi
S
S
Allavena
P
P
Sozzani
S
S
Mantovani
A
A
Balkwill
F R
FR
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001201:Ascites; D001483:Base Sequence; D002460:Cell Line; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000032:analysis* / Q000096:biosynthesis*; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000032:analysis*; D017931:DNA Primers; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010053:Ovary / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D014183:Transplantation, Heterologous
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger