Molecular abnormalities in the epithelial cells of
endometriosis and their relevance to
carcinogenesis of the ovary have been well studied. On the other hand, the differences of proinflammatory microenvironments between
endometriosis and ovarian
carcinomas have not been well documented yet. In this study, the expression patterns of
CXC chemokines (IL-8, ENA-78, GRO-alpha, I-TAC, Mig, and SDF-1) and their
receptors (CXCR2, CXCR3, and CXCR4) were compared among 12 ovarian
carcinomas, 8
endometriosis, and 6 normal ovaries using quantitative
reverse transcriptase polymerase chain reaction and immunohistochemistry. The CXCR3-mediated signaling in ovarian
carcinoma cells in vitro was also investigated. In quantitative
reverse transcriptase polymerase chain reaction, ENA-78 was up-regulated both in
endometriosis and
carcinomas, whereas I-TAC was detected exclusively in
carcinomas. CXCR3 was up-regulated both in
carcinomas and
endometriosis. However, immunohistochemical studies revealed that the localization of CXCR3 in
carcinomas was distinctively different from that in
endometriosis. In
carcinoma-
endometriosis coexisting cases, CXCR3-positive lymphocytes in benign lesions decreased in proportion as CXCR3-positive
tumor cells replaced the tissues. CXCR3 was also detected in ovarian
carcinoma cell lines in vitro. Administration of
interferon gamma (IFN-gamma)-inducible
chemokines induced
extracellular signal-regulated kinase phosphorylation in these
carcinoma cells. The results indicated that
CXC chemokines might contribute to the progression of ovarian
carcinomas and
endometriosis in different manners. Aberrant expression of IFN-gamma-inducible
chemokines and CXCR3 in
carcinoma cells in association with reduced CXCR3-positive immune cells raised the possibility that IFN-gamma-inducible
chemokines might not exert effective antitumor immune responses but that they might work in favor of
tumor progression.