Bone marrow-derived mesenchymal stem cell-secreted IL-8 promotes the angiogenesis and growth of colorectal cancer
2015; Impact Journals LLC; Volume: 6; Issue: 40 Linguagem: Inglês
10.18632/oncotarget.5739
ISSN1949-2553
AutoresJiancheng Wang, Yingnan Wang, Shao‐Chuan Wang, Jianye Cai, Jianqiang Shi, Xin Sui, Yong Cao, Weijun Huang, Xiaoyong Chen, Zijie Cai, Hongyu Li, Adham Sameer A. Bardeesi, Bin Zhang, Muyun Liu, Song Wu, Maosheng Wang, Andy Peng Xiang,
Tópico(s)Immune cells in cancer
Resumo// 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.
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