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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 .

Infiltration of tumor‐associated macrophages is involved in CD 44 expression in clear cell renal cell carcinoma