Granulocyte colony-stimulating factor promotes tumor angiogenesis via increasing circulating endothelial progenitor cells and Gr1+CD11b+cells in cancer animal models
Granulocyte colony-stimulating factor promotes tumor angiogenesis via increasing circulating endothelial progenitor cells and Gr1+CD11b+cells in cancer animal models
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DOI：
10.1093/intimm/dxh334
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发表时间：
2006-01-01
影响因子：
4.4
通讯作者：
Yamaya, M
中科院分区：
文献类型：
--
作者：
Okazaki, T;Ebihara, S;Yamaya, M
重组粒细胞集落刺激因子（G-CSF）用于化疗引起的骨髓抑制的癌症患者。已有报道G-CSF可促进肿瘤生长和血管生成，但G-CSF激活肿瘤血管生成的确切机制尚未完全阐明。N-末端突变的重组人G-CSF给药增加外周血WBC和中性粒细胞，减少小鼠骨髓基质细胞衍生因子-1，表明其生物学相关性。用刘易斯肺癌细胞（LLC）或KLN 205细胞接种小鼠并用G-CSF处理。G-CSF促进肿瘤生长和肿瘤内血管密度，而它不促进LLCs，KLN 205细胞和人脐静脉内皮细胞的增殖。在没有肿瘤的情况下，G-CSF没有增加显示内皮祖细胞（EPCs）表型特征的循环细胞。在肿瘤的存在下，G-CSF增加循环EPCs。此外，G-CSF治疗增加了荷瘤小鼠的免疫抑制和内皮细胞分化Gr 1 + CD 11b+细胞。我们的结论是，G-CSF促进肿瘤生长，通过激活肿瘤血管生成，通过增加循环EPCs和Gr 1 + CD 11b+细胞在癌症动物模型。
Recombinant granulocyte colony-stimulating factor (G-CSF) is used for cancer patients with myelosuppression induced by chemotherapy. G-CSF has been reported to progress tumor growth and angiogenesis, but the precise mechanism of tumor angiogenesis activated by G-CSF has not been fully clarified. N-terminal-mutated recombinant human G-CSF administration increased WBCs and neutrophils in peripheral blood and reduced bone marrow stromal cell-derived factor-1 in mice, indicating its biological relevance. Mice were inoculated with Lewis lung carcinoma cells (LLCs) or KLN205 cells and treated with G-CSF. G-CSF accelerated tumor growth and intratumoral vessel density, while it did not accelerate proliferation of LLCs, KLN205 cells or human umbilical vein endothelial cells in vitro. In the absence of tumors, G-CSF did not increase circulating cells that displayed phenotypic characteristics of endothelial progenitor cells (EPCs). In the presence of tumors, G-CSF increased circulating EPCs. In addition, G-CSF treatment increased immune suppressor and endothelial cell-differentiating Gr1+CD11b+ cells in tumor-bearing mice. We conclude that G-CSF promotes tumor growth by activating tumor angiogenesis via increasing circulating EPCs and Gr1+CD11b+ cells in cancer animal models.