title: Interactions between colon cancer cells and tumor-infiltrated macrophages depending on cancer cell-derived colony stimulating factor 1.
abstract: Tumor-infiltrated macrophages were potential targets of the immune therapy for patients with colon cancer. Colony stimulating factor 1 (CSF1) is a primary chemoattractant and functional regulator for macrophages, and therefore would be a feasible intervention for the macrophage-targeting therapeutics. However, the expression of CSF1 in colon cancer microenvironment and its roles in cancer development is largely unknown. In the present study, we found that CSF1 was over-expressed exclusively in colon cancer cells and was correlated with macrophages infiltration. The high CSF1 expression and macrophages infiltration were related to the tumor-node-metastasis (TNM) stage of colon cancer, and suggested to be positively associated with survival of colon cancer patients. In thein vitrostudies based on an indirect Transwell system, we found that co-culture with macrophage promoted CSF1 production in colon cancer cells. Further investigation on regulatory mechanisms suggested that CSF1 production in colon cancer cells was dependent on PKC pathway, which was activated by IL-8, mainly produced by macrophages. Moreover, colon cancer cell-derived CSF1 drove the recruitment of macrophages and re-educated their secretion profile, including the augment of IL-8 production. The mice tumor xenografts study also found that over-expression of CSF1 in colon cancer cells promoted intratumoral infiltration of macrophages, and partially suppressed tumor growth. In all, our results demonstrated that CSF1 was an important factor in the colon cancer microenvironment, involving in the interactions between colon cancer cells and tumor-infiltrated macrophages.
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University , Jinan, Shandong, China.
authors.forename: Huayang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University , Jinan, Shandong, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University , Jinan, Shandong, China.
authors.forename: Jintang
authors.initials: J
authors.lastname: Sun
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University , Jinan, Shandong, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University , Jinan, Shandong, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Gao
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University , Jinan, Shandong, China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University , Jinan, Shandong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, China; Biotherapy Research Center, Shandong University Nanshan Branch of Qilu Hospital, Yantai, Shandong, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
keywords: Colon cancer; colony stimulating factor 1; interleukin 8; macrophages; recruitment; survival