title: Chemokine CCL15 Mediates Migration of Human Bone Marrow-Derived Mesenchymal Stem Cells Toward Hepatocellular Carcinoma.
abstract: Mesenchymal stem cells (MSCs) possess the ability to migrate toward tumor sites and are regarded as promising gene delivery vehicles for cancer therapeutics. However, the factors that mediate this tropism have yet to be completely elucidated. In this study, through cytokine array analysis, chemokine CCL15 was found to be the most abundant protein differentially expressed in hepatocellular carcinoma (HCC) cell lines compared with a normal liver cell line. Serum CCL15 levels in HCC patients determined by enzyme linked immunosorbent assay were shown to be profoundly elevated compared with healthy controls. Immunohistochemical analysis indicated that CCL15 expression was much stronger in HCC tumor tissues than in adjacent nontumor tissues. Transwell migration assay suggested that CCL15 may be involved in chemotaxis of human MSCs (hMSCs) toward HCC in vitro and that this chemotactic effect of CCL15 is mediated via CCR1 receptors on hMSCs. Orthotopic animal models of HCC were established to investigate the role of CCL15 in hMSCs migration toward HCC in vivo. Both histological and flow cytometric analysis showed that significantly fewer hMSCs localized within 97H-CCL15-shRNA xenografts compared with 97H-green fluorescent protein xenografts after intravenous delivery. Finally, the possible effects of hMSCs on HCC tumor growth were also evaluated. Coculture experiments showed that hMSCs had no apparent effect on the proliferation of HCC cells in vitro In addition, systemic administration of hMSCs did not affect HCC tumor progression in vivo. Our data in this study help to elucidate the mechanism underlying the homing capacity of hMSCs toward HCC.
authors.affiliation: Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Orthopaedics, Jiangsu Provincial Hospital of Integrated Chinese and Western Medicine, Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Sen
authors.initials: S
authors.lastname: Lu
authors.affiliation: Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Xinli
authors.initials: X
authors.lastname: Huang
authors.affiliation: Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Runqiu
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Yao
authors.affiliation: Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Beicheng
authors.initials: B
authors.lastname: Sun
authors.affiliation: Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D002633:Chemotaxis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use; D054389:Receptors, CCR1 / Q000096:biosynthesis / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C108814:CCL15 protein, human; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D034741:RNA, Small Interfering; D054389:Receptors, CCR1; D049452:Green Fluorescent Proteins
keywords: CCL15; Chemotaxis; Hepatocellular carcinoma; Mesenchymal stem cells