Research Papers:

Neuroendocrine-like cells -derived CXCL10 and CXCL11 induce the infiltration of tumor-associated macrophage leading to the poor prognosis of colorectal cancer

Yu-Jie Zeng, Wei Lai, Heng Wu, Lu Liu, He-Yang Xu, Jie Wang and Zhong-Hua Chu _

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Oncotarget. 2016; 7:27394-27407. https://doi.org/10.18632/oncotarget.8423

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Yu-Jie Zeng1,*, Wei Lai1,*, Heng Wu1,*, Lu Liu1, He-Yang Xu1, Jie Wang1, Zhong-Hua Chu1

1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastroenteropancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Zhong-Hua Chu, e-mail: [email protected]

Keywords: colorectal cancer, neuroendocrine differentiation, tumor-associated macrophages, prognosis

Received: October 01, 2015     Accepted: March 17, 2016     Published: March 28, 2016


Our previous study revealed that neuroendocrine differentiation in colorectal cancer is one of the important factors leading to worse prognosis. In this study, we apply immunohistochemical staining, Western-blot, RT-PCR and ELISA to investigate the underlying mechanism that how the neuroendocrine differentiation to affect the prognosis of colorectal cancer. The interaction of colorectal cancer cells, neuroendocrine-like cells and tumor-associated macrophages in colorectal cancer progress is also investigated. By analyzing 82 cases of colorectal cancer patients treated in our institution, we found that colorectal adenocarcinoma with neuroendocrine differentiation had increasing number of tumor-associated macrophages and worse prognosis. Further evaluation of cytology showed that neuroendocrine cells have the ability to recruit tumor-associated macrophages to infiltrate the tumor tissue, and the tumor-associated macrophages enhance the proliferation and invasion abilities of the colon cancer cells. Moreover, we confirmed that CXCL10 and CXCL11 are the key chemokines in neuroendocrine-like cells and they promote the chemotaxis activity of tumor-associated macrophages. The secretion of CXCL10 and CXCL11 by neuroendocrine-like cells can recruit tumor-associated macrophages to infiltrate in tumor tissues. The latter enhances the proliferation and invasion of colorectal cancer cell and lead to poor prognosis.

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