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イツミ モモエ
逸見 百江 所属 川崎医科大学 医学部 一般教養 自然科学 職種 助教 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Coculture in vitro with endothelial cells induces cytarabine resistance of acute myeloid leukemia cells in a VEGF-A/VEGFR-2 signaling-independent manner. |
| 掲載誌名 | 正式名：Biochemical and biophysical research communications 略 称：Biochem Biophys Res Commun ISSNコード：10902104/0006291X |
| 掲載区分 | 国外 |
| 巻・号・頁 | 587,pp.78-84 |
| 著者・共著者 | Shuichiro Okamoto, Kei Miyano, Keisuke Kitakaze, Hitomi Kato, Akira Yamauchi, Mizuho Kajikawa, Momoe Itsumi, Chikage Kawai, Futoshi Kuribayashi |
| 発行年月 | 2022/01 |
| 概要 | An interaction between acute myeloid leukemia (AML) cells and endothelial cells in the bone marrow seems to play a critical role in chemosensitivity on leukemia treatment. The endothelial niche reportedly enhances the paracrine action of the soluble secretory proteins responsible for chemoresistance in a vascular endothelial growth factor A (VEGF-A)/VEGF receptor 2 (VEGFR-2) signaling pathway-dependent manner. To further investigate the contribution of VEGF-A/VEGFR-2 signaling to the chemoresistance of AML cells, a biochemical assay system in which the AML cells were cocultured with human endothelial EA.hy926 cells in a monolayer was developed. By coculture with EA.hy926 cells, this study revealed that the AML cells resisted apoptosis induced by the anticancer drug cytarabine. SU4312, a VEGFR-2 inhibitor, attenuated VEGFR-2 phosphorylation and VEGF-A/VEGFR-2 signaling-dependent endothelial cell migration; thus, this inhibitor was observed to block VEGF-A/VEGFR-2 signaling. Interestingly, this inhibitor did not reverse the chemoresistance. When VEGFR-2 was knocked out in EA.hy926 cells using the CRISPR-Cas9 system, the cytarabine-induced apoptosis of AML cells did not significantly change compared with that of wild-type cells. Thus, coculture-induced chemoresistance appears to be independent of VEGF-A/VEGFR-2 signaling. When the transwell, a coculturing device, separated the AML cells from the EA.hy926 cells in a monolayer, the coculture-induced chemoresistance was inhibited. Given that the migration of VEGF-A/VEGFR-2 signaling-dependent endothelial cells is necessary for the endothelial niche formation in the bone marrow, VEGF-A/VEGFR-2 signaling contributes to chemoresistance by mediating the niche formation process, but not to the chemoresistance of AML cells in the niche. |
| DOI | 10.1016/j.bbrc.2021.11.090 |
| PMID | 34872003 |