Bone marrow-derived mesenchymal stem cell-secreted IL-8 promotes the angiogenesis and growth of colorectal cancer

Abstract

// Jiancheng Wang 1, 2, * , Yingnan Wang 2, * , Shaochuan Wang 3, * , Jianye Cai 1, 2 , Jianqiang Shi 4 , Xin Sui 5 , Yong Cao 6 , Weijun Huang 2 , Xiaoyong Chen 2 , Zijie Cai 2 , Hongyu Li 2 , Adham Sameer A. Bardeesi 2 , Bin Zhang 2 , Muyun Liu 2 , Wu Song 3 , Maosheng Wang 6 , Andy Peng Xiang 1, 2, 7 1 The Biotherapy Center, The Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China 2 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, China 3 Department of Gastrointestinal-Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China 4 Department of Radiology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China 5 Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University Medical College, Xi’an, Shaanxi, China 6 The Cardiovascular Center, Gaozhou People’s Hospital, Maoming, Guangdong, China 7 Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China * These authors have contributed equally to this work Correspondence to: Andy Peng Xiang, e-mail: xiangp@mail.sysu.edu.cn Maosheng Wang, e-mail: mmwmsmd@126.com Keywords: colorectal cancer, mesenchymal stem cells, interleukin-8, angiogenesis Received: June 04, 2015      Accepted: October 13, 2015      Published: October 23, 2015 ABSTRACT Mesenchymal stem cells (MSCs) have recently been shown to home to tumors and contribute to the formation of the tumor-associated stroma. In addition, MSCs can secrete paracrine factors to facilitate tumor progression. However, the involvement of MSC-derived cytokines in colorectal cancer (CRC) angiogenesis and growth has not been clearly addressed. In this study, we report that interleukin-8 (IL-8) was the most highly upregulated pro-angiogenic factor in MSCs co-cultured with CRC cells and was expressed at substantially higher levels in MSCs than CRC cells. To evaluate the effect of MSC-derived IL-8 on CRC angiogenesis and growth, we used MSCs that expressed small hairpin (interfering) RNAs (shRNA) targeting IL-8 (shIL-8-MSCs). We found that MSC-secreted IL-8 promoted human umbilical vein endothelial cell (HUVEC) proliferation and migration, tube-formation ability and CRC cell proliferation. Additionally, in vivo studies showed that MSCs promoted tumor angiogenesis partially through IL-8. Taken together, these findings suggest that IL-8 secreted by MSCs promotes CRC angiogenesis and growth and can therefore serve as a potential novel therapeutic target.