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CTHRC1 promotes M2-like macrophage recruitment and myometrial invasion in endometrial carcinoma by integrin-Akt signaling pathway

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Abstract

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.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (ID 81672564 to S. Zhang).

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  1. Lu-Ying Li and Ke-Min Yin have contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Shanghai Key Laboratory of Gynecology Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pu Jian Road, Shanghai, 200127, People’s Republic of China

    Lu-Ying Li, Ke-Min Yin, Yi-Han Bai, Wen Di & Shu Zhang

  2. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China

    Zhi-Gang Zhang

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Li, LY., Yin, KM., Bai, YH. et al. CTHRC1 promotes M2-like macrophage recruitment and myometrial invasion in endometrial carcinoma by integrin-Akt signaling pathway. Clin Exp Metastasis 36, 351–363 (2019). https://doi.org/10.1007/s10585-019-09971-4

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