Fujimoto Naohiro
   Department   School of Medicine  Urology, Clinical Medical Sciences
Article types journal article
Language English
Peer review Peer reviewed
Title Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma.
Journal Formal name:Cancer science
Abbreviation:Cancer Sci
ISSN code:13497006/13479032
Domestic / ForeginForegin
Volume, Issue, Page 107(5),700-7頁
Author and coauthor 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 date 2016/05
Summary 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 (ccRCC). Because the detailed mechanisms allowing the maintenance of CSC in cancer tissues remain unclear, we investigated the relationship between TAM and CD44-expressing cancer cells in ccRCC. CD44 was used as a marker for CSC, and CD163 and CD204 were used as markers for TAM. CD44-positive cancer cells were detected in 37 of the 103 cases. Although statistical analysis showed no relationship between CD44-positive cancer cells and the clinical course, the distribution of CD44-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 CD44 expression was upregulated by direct co-culture with macrophages. Silencing of TNF-alpha on macrophages abrogated the upregulation of CD44 expression in cancer cells. Macrophage-induced CD44 overexpression was also suppressed by NF-κB inhibitors. These results suggest that TNF-alpha derived from TAM is linked to CD44 overexpression via NF-κB signaling in ccRCC.
DOI 10.1111/cas.12917
PMID 26918621