Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma

Chaoya Ma, Yoshihiro Komohara, Koji Ohnishi, Tetsu Shimoji, Nao Kuwahara, Yasuo Sakumura, Kozue Matsuishi, Yukio Fujiwara, Takanobu Motoshima, Wataru Takahashi, Sohsuke Yamada, Shohei Kitada, Naohiro Fujimoto, Toshiyuki Nakayama, Masatoshi Eto, Motohiro Takeya

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Abstract

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. Cancer stem-like cells (CSCs) 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 (TAMs) are a main component of stromal cells and are related to cancer progression in clear cell renal cell carcinoma (ccRCC). Our findings suggest that TNF-alpha derived from TAMs is linked to CD44 overexpression via NF-kB signaling in ccRCC.

Original languageEnglish
Pages (from-to)700-707
Number of pages8
JournalCancer Science
Volume107
Issue number5
DOIs
Publication statusPublished - May 1 2016

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Renal Cell Carcinoma
Macrophages
Neoplasms
Neoplastic Stem Cells
Tumor Necrosis Factor-alpha
Stromal Cells
Hospital Distribution Systems
Recurrence
NF-kappa B
Tumor Biomarkers
Coculture Techniques

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Ma, C., Komohara, Y., Ohnishi, K., Shimoji, T., Kuwahara, N., Sakumura, Y., ... Takeya, M. (2016). Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma. Cancer Science, 107(5), 700-707. https://doi.org/10.1111/cas.12917

Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma. / 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.

In: Cancer Science, Vol. 107, No. 5, 01.05.2016, p. 700-707.

Research output: Contribution to journalArticle

Ma, C, Komohara, Y, Ohnishi, K, Shimoji, T, Kuwahara, N, Sakumura, Y, Matsuishi, K, Fujiwara, Y, Motoshima, T, Takahashi, W, Yamada, S, Kitada, S, Fujimoto, N, Nakayama, T, Eto, M & Takeya, M 2016, 'Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma', Cancer Science, vol. 107, no. 5, pp. 700-707. https://doi.org/10.1111/cas.12917
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. / Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma. In: Cancer Science. 2016 ; Vol. 107, No. 5. pp. 700-707.
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