title: Bone marrow-derived mesenchymal stem cell-secreted IL-8 promotes the angiogenesis and growth of colorectal cancer.
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.
authors.affiliation: The Biotherapy Center, The Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.|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.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal-Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Shaochuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: The Biotherapy Center, The Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.|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.
authors.forename: Jianye
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Radiology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shaanxi, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sui
authors.affiliation: The Cardiovascular Center, Gaozhou People's Hospital, Maoming, Guangdong, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Zijie
authors.initials: Z
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Adham Sameer A
authors.initials: AS
authors.lastname: Bardeesi
authors.affiliation: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Muyun
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal-Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Song
authors.affiliation: The Cardiovascular Center, Gaozhou People's Hospital, Maoming, Guangdong, China.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Wang
authors.affiliation: The Biotherapy Center, The Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.|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.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D064593:Heterografts; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: C508606:CXCL8 protein, human; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D034741:RNA, Small Interfering
keywords: angiogenesis; colorectal cancer; interleukin-8; mesenchymal stem cells