Bone marrow-derived mesenchymal stem cell-secreted IL-8 promotes the angiogenesis and growth of colorectal cancer
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Jiancheng Wang1,2,*, Yingnan Wang2,*, Shaochuan Wang3,*, Jianye Cai1,2, Jianqiang Shi4, Xin Sui5, Yong Cao6, Weijun Huang2, Xiaoyong Chen2, Zijie Cai2, Hongyu Li2, Adham Sameer A. Bardeesi2, Bin Zhang2, Muyun Liu2, Wu Song3, Maosheng Wang6, Andy Peng Xiang1,2,7
1The Biotherapy Center, The Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China
2Center 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
3Department of Gastrointestinal-Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
4Department of Radiology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
5Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University Medical College, Xi’an, Shaanxi, China
6The Cardiovascular Center, Gaozhou People’s Hospital, Maoming, Guangdong, China
7Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China
*These authors have contributed equally to this work
Andy Peng Xiang, e-mail: [email protected]
Maosheng Wang, e-mail: [email protected]
Keywords: colorectal cancer, mesenchymal stem cells, interleukin-8, angiogenesis
Received: June 04, 2015 Accepted: October 13, 2015 Published: October 23, 2015
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.
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