title: Tumor-derived mural-like cells coordinate with endothelial cells: role of YKL-40 in mural cell-mediated angiogenesis.
abstract: Tumor neo-vasculature is characterized by spatial coordination of endothelial cells with mural cells, which delivers oxygen and nutrients. Here, we explored a key role of the secreted glycoprotein YKL-40, a mesenchymal marker, in the interaction between endothelial cells and mesenchymal mural-like cells for tumor angiogenesis. Xenotransplantation of tumor-derived mural-like cells (GSDCs) expressing YKL-40 in mice developed extensive and stable blood vessels covered with more GSDCs than those in YKL-40 gene knockdown tumors. YKL-40 expressed by GSDCs was associated with increased interaction of neural cadherin/β-catenin/smooth muscle alpha actin; thus, mediating cell-cell adhesion and permeability. YKL-40 also induced the interaction of vascular endothelial cadherin/β-catenin/actin in endothelial cells (HMVECs). In cell co-culture systems, YKL-40 enhanced both GSDC and HMVEC contacts, restricted vascular leakage, and stabilized vascular networks. Collectively, the data inform new mechanistic insights into the cooperation of mural cells with endothelial cells induced by YKL-40 during tumor angiogenesis, and also enhance our understanding of YKL-40 in both mural and endothelial cell biology.
authors.affiliation: Molecular and Cellular Biology Program, Morrill Science Center, University of Massachusetts, Amherst, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Francescone
authors.affiliation: Graduate School, Khon Khaen University, Khon Khaen, Thailand.
authors.forename: N
authors.initials: N
authors.lastname: Ngernyuang
authors.affiliation: Pioneer Valley Life Sciences Institute, Springfield, MA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Yan
authors.affiliation: Pioneer Valley Life Sciences Institute, Springfield, MA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Bentley
authors.affiliation: 1] Molecular and Cellular Biology Program, Morrill Science Center, University of Massachusetts, Amherst, MA, USA [2] Pioneer Valley Life Sciences Institute, Springfield, MA, USA [3] Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Shao
mesh_terms: D000199:Actins / Q000378:metabolism; D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D000071451:Chitinase-3-Like Protein 1; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009130:Muscle, Smooth / Q000737:chemistry; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020286:Pericytes / Q000378:metabolism* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D034622:RNA Interference; D014183:Transplantation, Heterologous; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000199:Actins; D054392:Adipokines; C084533:CHI3L1 protein, human; D015820:Cadherins; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051176:beta Catenin