Open AccessInfiltration of tumor‐associated macrophages is involved in CD 44 expression in clear cell renal cell carcinoma
Author(s) -
Ma Chaoya,
Komohara Yoshihiro,
Ohnishi Koji,
Shimoji Tetsu,
Kuwahara Nao,
Sakumura Yasuo,
Matsuishi Kozue,
Fujiwara Yukio,
Motoshima Takanobu,
Takahashi Wataru,
Yamada Sohsuke,
Kitada Shohei,
Fujimoto Naohiro,
Nakayama Toshiyuki,
Eto Masatoshi,
Takeya Motohiro
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12917
Subject(s) - cancer research , stromal cell , cancer cell , cancer , downregulation and upregulation , population , renal cell carcinoma , cell , cancer stem cell , tumor necrosis factor alpha , biology , medicine , pathology , immunology , biochemistry , genetics , environmental health , gene
Cancer stem‐like cells ( CSC ) or cancer‐initiating cells are now considered to be an important cell population related to cancer recurrence and the resistance to anti‐cancer therapy. Tumor‐associated macrophages ( TAM ) are a main component of stromal cells and are related to cancer progression in clear cell renal cell carcinoma (cc RCC ). Because the detailed mechanisms allowing the maintenance of CSC in cancer tissues remain unclear, we investigated the relationship between TAM and CD 44‐expressing cancer cells in cc RCC . CD 44 was used as a marker for CSC , and CD 163 and CD 204 were used as markers for TAM . CD 44‐positive cancer cells were detected in 37 of the 103 cases. Although statistical analysis showed no relationship between CD 44‐positive cancer cells and the clinical course, the distribution of CD 44‐positive cancer cells was significantly associated with a high density of TAM . Our in vitro study using RCC cell lines and human macrophages demonstrated that CD 44 expression was upregulated by direct co‐culture with macrophages. Silencing of TNF ‐alpha on macrophages abrogated the upregulation of CD 44 expression in cancer cells. Macrophage‐induced CD 44 overexpression was also suppressed by NF ‐κB inhibitors. These results suggest that TNF ‐alpha derived from TAM is linked to CD 44 overexpression via NF ‐κB signaling in cc RCC .