| RRC ID |
51692
|
| 著者 |
Naito H, Wakabayashi T, Kidoya H, Muramatsu F, Takara K, Eino D, Yamane K, Iba T, Takakura N.
|
| タイトル |
Endothelial Side Population Cells Contribute to Tumor Angiogenesis and Antiangiogenic Drug Resistance.
|
| ジャーナル |
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.
|
| 巻・号 |
76(11)
|
| ページ |
3200-10
|
| 公開日 |
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 |
9.727
|
| 引用数 |
35
|
| リソース情報 |
| ヒト・動物細胞 |
LLC(RCB0558)
KLN205(RCB2623)
OP9(RCB1124) |
