文献类型：期刊文献

英文题名：IL-8/CXCR2 mediates tropism of human bone marrow-derived mesenchymal stem cells toward CD133+/CD44+Colon cancer stem cells

作者：Ma, Xiaoying[1,2];Chen, Jingyun[1,2];Liu, Jiajun[1,2];Xu, Baixue[1,2];Liang, Xinyu[1,2];Yang, Xiaotong[1,2];Feng, Yun[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 Jiao Tong Univ, Dept Resp & Crit Care Med, Shanghai, Peoples R China

年份：2021

卷号：236

期号：4

起止页码：3114

外文期刊名：JOURNAL OF CELLULAR PHYSIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000579388000001)】；

基金：National Natural Science Foundation of China, Grant/Award Number: 81873050

语种：英文

外文关键词：colon cancer stem cell; CXCR2 inhibitor; IL-8 peptide inhibitor; mesenchymal stem cell; stemness; tropism

摘要：In cancer treatment, the most attractive feature of mesenchymal stem cells (MSCs) is it's homing to tumor tissues. MSC is an important part of the "colon cancer stem cell niche", but little research has been done on the tropism of human MSCs toward colon cancer stem cells (CCSCs). In this study, we first compared the effects of three tissue-derived MSCs (bone marrow, adipose tissue, and placenta) in vivo on colon tumor xenograft growth. Then, we analyzed the tropism of bone marrow-derived MSCs (BMSCs) toward normal intestinal epithelial cells (NCM460), parental colon cancer cells, CD133(-)/CD44(-,)and CD133(+)/CD44(+)colon cancer cells in vitro. Microarray analysis and in vitro experiments explored the mechanism of mediating the homing of BMSCs toward CCSCs. Compared with the parental and CD133(-)/CD44(-)colon cancer cells, CD133(+)/CD44(+)cells have a stronger ability to recruit BMSCs. In addition, BMSCs were significantly transformed into cancer-associated fibroblasts after being recruited by CCSCs. After coculture of BMSCs and CCSCs, the expression of interleukin (IL)-6, IL-8, IL-32, and CCL20 was significantly increased. Compared with parental strains, CD133(-)/CD44(-)cells, and NCM460, BMSC secreted significantly more IL-8 after coculture with CD133(+)/CD44(+)cells. Low concentration of IL-8 peptide inhibitors (100 ng/ml) and CXC receptor 2 (CXCR2) inhibitors have little effect on the migration of BMSCs, but can effectively weaken CCSC stemness and promote dormant CSCs in the coculture system to re-enter into the cell cycle. The endogenous IL-8 knockout in BMSCs or BMSCs loaded with IL-8 and/or CXCR2 inhibitors will make the therapy of BMSC targeting CCSCs function at its best.