RRC ID 38428
Author Kidoya H, Kunii N, Naito H, Muramatsu F, Okamoto Y, Nakayama T, Takakura N.
Title The apelin/APJ system induces maturation of the tumor vasculature and improves the efficiency of immune therapy.
Journal Oncogene
Abstract Immature and unstable tumor vasculature provides an aberrant tumor microenvironment and leads to resistance of tumors to conventional therapy. Hence, normalization of tumor vessels has been reported to improve the effect of immuno-, chemo- and radiation therapy. However, the humoral factors, which can effectively induce maturation of tumor vasculature, have not been elucidated. In this study, we found that the novel peptide apelin and its receptor APJ can induce the morphological and functional maturation of blood vessels in tumors. This apelin-induced tumor vascular maturation enhances the efficacy of cancer dendritic cell-based immunotherapy and significantly suppresses tumor growth by promoting the infiltration of invariant natural killer T cells into the central region of the tumor and thereby robustly inducing apoptosis of tumor cells. Additionally, we showed APJ expression to be enhanced in the tumor endothelium in comparison with normal-state endothelial cells. These findings provide a new target for tumor vascular-specific maturation, which is expected to improve the efficacy of conventional cancer therapies.
Volume 31(27)
Pages 3254-64
Published 2012-7-5
DOI 10.1038/onc.2011.489
PII onc2011489
PMID 22037214
MeSH Animals Apelin Apelin Receptors Blood Vessels / drug effects Blood Vessels / metabolism Blood Vessels / physiopathology Bone Marrow Cells / cytology Cell Proliferation / drug effects Cell Transplantation Combined Modality Therapy Dendritic Cells / drug effects Dendritic Cells / immunology Dendritic Cells / transplantation Endothelial Cells / drug effects Endothelial Cells / metabolism Galactosylceramides / pharmacology Gene Expression Regulation, Neoplastic / drug effects Humans Immunotherapy* Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* Mice Natural Killer T-Cells / drug effects Natural Killer T-Cells / immunology Neoplasms / blood supply* Neoplasms / immunology Neoplasms / metabolism Neoplasms / therapy* Neovascularization, Pathologic / immunology Neovascularization, Pathologic / metabolism Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / metabolism* Treatment Outcome
IF 6.854
Times Cited 22
Human and Animal Cells