Endothelial Side Population Cells Contribute to Tumor Angiogenesis and Antiangiogenic Drug Resistance
| Autor: | Taku Wakabayashi, Daisuke Eino, Fumitaka Muramatsu, Keitaro Yamane, Tomohiro Iba, Kazuhiro Takara, Nobuyuki Takakura, Hiroyasu Kidoya, Hisamichi Naito |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Pathology medicine.medical_specialty Endothelium Angiogenesis Blotting Western Population Fluorescent Antibody Technique Angiogenesis Inhibitors Apoptosis Immunoenzyme Techniques Neovascularization Carcinoma Lewis Lung Mice 03 medical and health sciences In vivo Neoplasms Tumor Cells Cultured Animals Medicine education Side-Population Cells Cell Proliferation education.field_of_study Neovascularization Pathologic business.industry Cancer medicine.disease Mice Inbred C57BL Haematopoiesis 030104 developmental biology medicine.anatomical_structure Oncology Drug Resistance Neoplasm Cancer research Endothelium Vascular medicine.symptom business Blood vessel |
| Zdroj: | Cancer Research. 76:3200-3210 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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