title: The mobilization, recruitment and contribution of bone marrow-derived             endothelial progenitor cells to the tumor neovascularization occur at an early             stage and throughout the entire process of hepatocellular carcinoma growth.
abstract: Obvious neovascularization is a key feature of hepatocellular carcinoma             (HCC) and the status of neovascularization in HCC is closely correlated with the             tumor growth and patient prognosis. The actual effect of current antivascular             treatment including embolization to HCC is not satisfactory. Compensatory angiogenesis             is one of the primary causes responsible for failure of antiangiogenic therapy.             Bone marrow-derived endothelial progenitor cells (BM-EPCs) are considered as important             building blocks for adult neovascularization. However, the role of mobilized BM-EPCs             in HCC remains unknown. In this study, GFP+-BM orthotropic HCC mice were established             to investigate whether BM-EPCs are involved in HCC-induced neovascularization.             We found that a large number of BM-EPCs were mobilized into the circulation with             the development of HCC, recruited into the HCC region and incorporated into the             vascular endothelium directly by differentiation into vascular endothelial cells,             including sinus, capillary vessels and great vessels. Dynamic observation revealed             that the mobilization and the incorporation of BM-EPCs into different types of             vessels were present in early phases and throughout the whole process of HCC growth.             The proportion of BM-EPCs in vessels increased gradually, from 17 to 21% with             tumor growth. Moreover, injected GFP+-EPCs also specifically homed to tumor tissue             and incorporated into tumor vessels directly. In this initial study, we demonstrated             that BM-EPCs play a prominent role in HCC neovascularization. Blockade of BM-EPC-mediated             vasculogenesis may improve the efficacy of current anti-vascularization therapy             for patients with HCC.
authors.affiliation: Institute of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, The Affiliated DrumTower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, PR China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhu
authors.forename: Qianwen
authors.initials: Q
authors.lastname: Shao
authors.forename: Xitai
authors.initials: X
authors.lastname: Sun
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Deng
authors.forename: Xianwen
authors.initials: X
authors.lastname: Yuan
authors.forename: Decai
authors.initials: D
authors.lastname: Yu
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.forename: Yitao
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D001775:Blood Circulation; D001853:Bone Marrow / Q000473:pathology*; D002196:Capillaries / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D042783:Endothelial Cells / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000378:metabolism; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C090509:Icam1 protein, mouse; D010455:Peptides; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D018799:Intercellular Adhesion Molecule-1; D049452:Green Fluorescent Proteins