Impaired CXCL4 expression in tumor-associated macrophages (TAMs) of ovarian cancers arising in endometriosis

Mitsuko Furuya, Reiko Tanaka, Etsuko Miyagi, Daisuke Kami, Kiyotaka Nagahama, Yohei Miyagi, Yoji Nagashima, Fumiki Hirahara, Yoshiaki Inayama, Ichiro Aoki
Cancer biology & therapy · 2012 · vol. 13(8) , pp. 671–680 · doi:10.4161/cbt.20084 · PMID:22555803 · W2075567711
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Tumor-associated macrophages in ovarian cancers arising from endometriosis exhibit impaired expression of CXCL4 compared to those in endometriosis lesions.

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Abstract

Inflammatory cells play important roles in progression of solid neoplasms including ovarian cancers. Tumor-associated macrophages (TAMs) contribute to angiogenesis and immune suppression by modulating microenvironment. Ovarian cancer develops occasionally on the bases of endometriosis, a chronic inflammatory disease. We have recently demonstrated differential expressions of CXCR3 variants in endometriosis and ovarian cancers. In this study, we showed impaired CXCL4 expression in TAMs of ovarian cancers arising in endometriosis. The expressions of CXCL4 and its variant CXCL4L1 were investigated among normal ovaries (n = 26), endometriosis (n = 18) and endometriosis-associated ovarian cancers (EAOCs) composed of clear cell (n = 13) and endometrioid (n = 11) types. In addition, four cases of EAOCs that contained both benign and cancer lesions contiguously in single cysts were investigated in the study. Western blot and quantitative RT-PCR analyses revealed significant downregulation of CXCL4 and CXCL4L1 in EAOCs compared with those in endometriosis. In all EAOCs coexisting with endometriosis in the single cyst, the expression levels of CXCL4 and CXCL4L1 were significantly lower in cancer lesions than in corresponding endometriosis. Histopathological study revealed that CXCL4 was strongly expressed in CD68 (+) infiltrating macrophages of endometriosis. In microscopically transitional zone between endometriosis and EAOC, CD68 (+) macrophages often demonstrated CXCL4 (-) pattern. The majority of CD68 (+) TAMs in overt cancer lesions were negative for CXCL4. Collective data indicate that that CXCL4 insufficiency may be involved in specific inflammatory microenvironment of ovarian cancers arising in endometriosis. Suppression of CXCL4 in cancer lesions is likely to be attributable to TAMs in part.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometriosis Gene Expression Regulation Macrophages Ovarian Neoplasms Ovarian Neoplasms Platelet Factor 4 Adult Aged Endometriosis Endometriosis Female Humans Macrophages Middle Aged Ovarian Neoplasms Ovarian Neoplasms Platelet Factor 4 Platelet Factor 4 Protein Transport

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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