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癌再発・進展における血管内皮前駆細胞の役割

血管内皮祖细胞在癌症复发和进展中的作用

基本信息

批准号：
18790994
负责人：
上田和弘
金额：
$ 1.98万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18790994/
关键词：
Endotheial progenitor cell Chemotherapy CXCR4 癌化学療法血管再生血管内皮前駆細胞

项目摘要

C57BL/6マウスにcyclophosphamide(以下CTX)あるいは生理食塩水を腹腔内投与し、7,14,21日目に末梢血中のCD34、flk-1陽敗細胞数をflow cytometiy で測定した。GFP陽性骨髄細胞を移植したキメラマウスを用いて、CTXあるいは生理食塩水を腹腔内投与後にLewis肺癌細胞5×106個を皮下投与した腫瘍モデルを作製した。腫瘍移植後4, 6, 8,10日目に血管内皮前駆細胞の末梢への動員を制御する目的で抗CXCR4抗体を腹腔内投与した。移植後14日目に腫瘍を摘出し重量を測定した。腫瘍血管密度、細胞の増殖、腫瘍組織内の骨髄由来GFP陽敗細胞数および血管内皮細胞への分化を組織学的に定量評価した。その結果、末梢血中のCD34陽僧投与群は生食投与群と比べ、腫瘍重量が約1.3倍に増大し、腫瘍血管密度、腫瘍細胞増殖率、およびGFP陽陛血管内皮細胞数はいずれも高値を示した(全てp<0.05)。一方、CTX投与後の抗CXCR4抗体併用により、腫瘍の増大は抑制され、腫瘍血管密度、腫瘍細胞増殖率、腫瘍内GFP陽性細胞数およびGFP陽敗血管内皮細胞数はいずれも低値を示した(全てp<0.05)。以上より、化学療法後の癌再増大において血管内皮前駆細胞は重要な役割を果たしており、同細胞を標的とした新しい癌治療戦略の合理性が示された。

The number of CD34 and flk-1 in peripheral blood was measured by flow cytometiy assay after intraperitoneal injection of C57BL/6, CD34 and flk-1 in peripheral blood on the 21st day. GFP bone allografts were implanted intraperitoneally with 5 × 10 6 cells of Lewis lung cancer, and then 5 × 10 6 cells of Lewis lung cancer were subcutaneously injected into the abdominal cavity. On the 4th, 6th, 8th and 10th day after transplantation, vascular endothelial precursors were injected intraperitoneally with anti-CXCR4 antibody. The weight was measured 14 days after transplantation. The blood vessel density, cellular proliferation and bone marrow in the tissue were determined by GFP. The number of cells and the histology of differentiation and differentiation of vascular endothelial cells were measured. The results showed that the blood vessel density, cell proliferation rate and endothelial cell count of CD34 monks in peripheral blood were significantly higher than those in GFP monks (P < 0.05). On the one hand, the anti-CXCR4 antibody was injected with CTX, and the blood vessel density, cell proliferation rate, GFP cell count, GFP cell count, endothelial cell count and low cell count of anti-GFP antibody were detected. After the above and chemical methods, the cancer is greatly affected, and the vascular endothelial precursors are important to be removed, and the cancer treatment is slightly reasonable and reasonable.