Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma.
Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma.
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DOI：
10.1111/cas.12917
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发表时间：
2016-05
期刊：
影响因子：
5.7
通讯作者：
Takeya M
中科院分区：
文献类型：
--
作者：
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
癌症干细胞样细胞（CSC）或癌症起始细胞现在被认为是与癌症复发和抗癌治疗耐药相关的重要细胞群。肿瘤相关巨噬细胞（TAM）是基质细胞的主要成分，与透明细胞肾细胞癌（ccRCC）的癌症进展相关。由于癌症组织中 CSC 维持的详细机制仍不清楚，因此我们研究了 ccRCC 中 TAM 和表达 CD44 的癌细胞之间的关系。 CD44用作CSC的标记物，CD163和CD204用作TAM的标记物。 103 例中有 37 例检测到 CD44 阳性癌细胞。尽管统计分析显示CD44阳性癌细胞与临床病程之间没有关系，但CD44阳性癌细胞的分布与高密度TAM显着相关。我们使用 RCC 细胞系和人巨噬细胞的体外研究表明，通过与巨噬细胞直接共培养，CD44 表达上调。巨噬细胞上 TNF-α 的沉默消除了癌细胞中 CD44 表达的上调。巨噬细胞诱导的 CD44 过度表达也被 NF-κB 抑制剂抑制。这些结果表明，源自 TAM 的 TNF-α 通过 ccRCC 中的 NF-κB 信号传导与 CD44 过度表达相关。
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.