文献类型：期刊文献

英文题名：Feature article: Mesenchymal stem cells maintain the stemness of colon cancer stem cells via interleukin-8/mitogen-activated protein kinase signaling pathway

作者：Ma, Xiaoying[1,2];Liu, Jiajun[1,2];Yang, Xiaotong[1,2];Fang, Kai[1,2];Zheng, Peiyong[3];Liang, Xin[1,2];Liu, Jianwen[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Longhua Hosp, Inst Digest Dis, Shanghai 200032, Peoples R China

年份：2020

卷号：245

期号：6

起止页码：562

外文期刊名：EXPERIMENTAL BIOLOGY AND MEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000523921400007)】；

语种：英文

外文关键词：Mesenchymal stem cell; colon cancer stem cell; stemness; interleukin-8; mitogen-activated protein kinase

摘要：Mesenchymal stem cells (MSCs) can act as a carrier in tumor therapy, and tumor suppressor gene-modified MSCs can reach and suppress the tumor. However, in the colon cancer microenvironment, MSCs could promote tumor growth and create the environment that is conducive to the survival of cancer stem cells (CSCs). This study discovered MSCs from three sources (bone marrow, adipose, placenta) could induce the stemness and epithelial-mesenchymal transition (EMT) of HCT116 in vitro, meanwhile adipose- and placenta-derived MSCs increase the proportion of CD133+/CD44+ HCT116. Then, we explored the interaction mechanism between CD133+/CD44+ HCT116 and MSCs by the bioinformatics and in vitro assays. After CD133+/CD44+ HCT116 were co-cultured with MSCs, many cytokines in MSCs were stimulated, including interleukin-8 (IL-8). The binding of IL-8/CXCR2 activates the downstream mitogen-activated protein kinase (MAPK) signaling pathway in colon CSCs, thereby promoting the stemness and EMT. However, inhibition of IL-8/CXCR2/Erk1/2 could reverse the effect of MSCs on CSC stemness. In addition, MSCs co-cultured with CD133+/CD44+ HCT116 produce a carcinoma-associated fibroblast phenotype via intracellular FGF10-PKA-Akt-beta-catenin signaling, which can be attenuated by IL-8 peptide inhibitor. To conclude, IL-8 promotes the interaction between colon CSCs and MSCs, and activates the MAPK signaling pathway in colon CSCs, which provides a theoretical basis for the application of MSCs in clinical practice. Impact statement MSCs have the property of chemotaxis and they can migrate to the tumor site by paracrine pathway in the tumor environment, and then interact with tumor cells. Although a mass of studies have been conducted about the impact of MSCs on tumors, it is still controversial whether the exogenous MSCs promote or inhibit tumor growth. In this work, we evaluated the effects of MSCs from three sources (bone marrow, adipose, placenta) on the proliferation, stemness, and metastasis of the colon cancer cells both in vitro and in vivo. Then, we proved the IL-8/CXCR2/MAPK and FGF10-PKA-Akt-beta-catenin signaling pathway which mediate the interplay between MSC and CD133+/CD44+ colon cancer cell. This research aims to provide a theoretical basis for the safe application of MSCs in the clinical treatment of colon cancer.