RRC ID 51692
Author Naito H, Wakabayashi T, Kidoya H, Muramatsu F, Takara K, Eino D, Yamane K, Iba T, Takakura N.
Title Endothelial Side Population Cells Contribute to Tumor Angiogenesis and Antiangiogenic Drug Resistance.
Journal Cancer Res
Abstract Angiogenesis plays a crucial role in tumor growth, with an undisputed contribution of resident endothelial cells (EC) to new blood vessels in the tumor. Here, we report the definition of a small population of vascular-resident stem/progenitor-like EC that contributes predominantly to new blood vessel formation in the tumor. Although the surface markers of this population are similar to other ECs, those from the lung vasculature possess colony-forming ability in vitro and contribute to angiogenesis in vivo These specific ECs actively proliferate in lung tumors, and the percentage of this population significantly increases in the tumor vasculature relative to normal lung tissue. Using genetic recombination and bone marrow transplant models, we show that these cells are phenotypically true ECs and do not originate from hematopoietic cells. After treatment of tumors with antiangiogenic drugs, these specific ECs selectively survived and remained in the tumor. Together, our results established that ECs in the peripheral vasculature are heterogeneous and that stem/progenitor-like ECs play an indispensable role in tumor angiogenesis as EC-supplying cells. The lack of susceptibility of these ECs to antiangiogenic drugs may account for resistance of the tumor to this drug type. Thus, inhibiting these ECs might provide a promising strategy to overcome antiangiogenic drug resistance. Cancer Res; 76(11); 3200-10. ©2016 AACR.
Volume 76(11)
Pages 3200-10
Published 2016-6-1
DOI 10.1158/0008-5472.CAN-15-2998
PII 0008-5472.CAN-15-2998
PMID 27197162
MeSH Angiogenesis Inhibitors / pharmacology* Animals Apoptosis Blotting, Western Carcinoma, Lewis Lung / blood supply* Carcinoma, Lewis Lung / drug therapy Carcinoma, Lewis Lung / pathology Cell Proliferation Drug Resistance, Neoplasm* Endothelium, Vascular / drug effects Endothelium, Vascular / pathology* Fluorescent Antibody Technique Immunoenzyme Techniques Mice Mice, Inbred C57BL Neoplasms / blood supply* Neoplasms / drug therapy Neoplasms / pathology Neovascularization, Pathologic / drug therapy Neovascularization, Pathologic / pathology* Side-Population Cells / drug effects Side-Population Cells / pathology* Tumor Cells, Cultured
IF 8.378
Times Cited 35
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