CTHRC1 promotes M2-like macrophage recruitment and myometrial invasion in endometrial carcinoma by integrin-Akt signaling pathway
CTHRC1 promotes M2-like macrophage recruitment and myometrial invasion in endometrial carcinoma by integrin-Akt signaling pathway
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CTHRC1通过整合素-Akt信号通路促进子宫内膜癌中M2样巨噬细胞的募集和肌层侵袭
DOI：
10.1007/s10585-019-09971-4
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发表时间：
2019-08-01
影响因子：
4
通讯作者：
Zhang, Shu
中科院分区：
文献类型：
--
作者：
Li, Lu-Ying;Yin, Ke-Min;Zhang, Shu
肿瘤相关巨噬细胞（tam）的浸润与子宫内膜癌（EC）的肿瘤进展和不良预后有关。胶原三螺旋重复含有1 （Collagen triple helix repeat containing 1, CTHRC1）是一种ECM分泌蛋白，已被报道在促进肿瘤侵袭和转移中发挥重要作用，但CTHRC1在EC中的功能作用及其与tam的关联尚不清楚。本文报道，在EC患者中，与正常子宫内膜相比，子宫内膜癌组织中CTHRC1表达上调（P < 0.0001），并与肿瘤分级和肌层浸润深度呈正相关（P = 0.024和P = 0.0002）。同时，CTHRC1表达与浸润性tam数量增加呈正相关（P = 0.003, P = 0.001）。在EC的肿瘤微环境中，CTHRC1不仅通过与Integrin β3-Akt信号通路相互作用促进肌层侵袭，还通过上调Fractalkine趋化因子受体（CX3CR1）在巨噬细胞中的表达，促进m2样tam的浸润。重组CTHRC1蛋白（rCTHRC1）水平的改变通过增强巨噬细胞的体外募集来促进肿瘤的迁移和侵袭。综上所述，我们的发现最终提供了CTHRC1在重塑肿瘤免疫微环境以促进EC患者肿瘤转移中的新作用。
The infiltration of tumor-associated macrophages (TAMs) is associated with tumor progression and poor prognosis in endometrial cancer (EC). Collagen triple helix repeat containing 1 (CTHRC1), a secreted ECM protein, has been reported to have important roles in promoting cancer invasion and metastasis, but the functional role of CTHRC1 and its association with TAMs in EC remain unclear. Here we report that, in EC patients, CTHRC1 expression was up-regulated in endometrial cancer tissues compared with normal endometrium (P < 0.0001), and is positively correlated with tumor grade and depth of myometrial invasion (P = 0.024 and P = 0.0002, respectively). Meanwhile, CTHRC1 expression was positively correlated with an increased number of infiltrating TAMs, especially M2-like TAMs (P = 0.003, P = 0.001). In the tumor microenvironment of EC, CTHRC1 not only promoted myometrial invasion by interacting with Integrin β3-Akt signaling pathway, but also promoted infiltration of M2-like TAMs by upregulating Fractalkine chemokine receptor (CX3CR1) expression in macrophages. Changing levels of recombinant CTHRC1 protein (rCTHRC1) promoted tumor migration and invasion via enhancing macrophage recruitment in vitro. In summary, our findings eventually provided a novel role for CTHRC1 in remodeling the tumor immune microenvironment to promote tumor metastasis in EC patients.