ImClone Systems Incorporated, New York, NY 10014, USA.
Curr Med Chem. 2009;16(22):2890-8. doi: 10.2174/092986709788803169.
The vascular endothelial growth factor (VEGF)/VEGF receptor pathways are essential for the regulation of angiogenesis during embryonic development and tumor progression. VEGF receptor 1 (VEGFR-1) has been shown to promote tumor growth and metastasis through the regulation of multiple biological functions in cancer cells, vasculature, stroma and other tumor-associated cells. VEGFR-1 signaling is required for the survival of endothelial cells and macrophages and the mobilization of cancer cells, endothelial cells, myeloid progenitors, and monocyte/macrophages. VEGFR-1 was reported to have a function in eliciting epithelial-to-mesenchymal transition in cancer cells toward invasive and metastatic phenotype. Furthermore, VEGFR-1 was found to promote metastasis through initiating pre-metastatic niche by VEGFR-1 positive bone marrow progenitors. It was reported that VEGFR-1 had an active role in promoting inflammation through modulating immune cells and mediating immunosuppression by VEGFR-1 positive myeloid cells. Given that VEGFR-1 has a multi-functional role in promoting angiogenesis, inflammation, tumor growth and metastasis, VEGFR-1 has emerged as a promising therapeutic target for treatment of cancer as well as angiogenesis and inflammation associated disorders.
血管内皮生长因子 (VEGF)/VEGF 受体途径对于胚胎发育和肿瘤进展过程中的血管生成的调节至关重要。已经表明,VEGF 受体 1 (VEGFR-1) 通过调节癌细胞、血管、基质和其他与肿瘤相关的细胞中的多种生物学功能,促进肿瘤的生长和转移。VEGFR-1 信号对于内皮细胞和巨噬细胞的存活以及癌细胞、内皮细胞、髓样祖细胞和单核细胞/巨噬细胞的动员是必需的。据报道,VEGFR-1 在诱导癌细胞向侵袭性和转移性表型的上皮-间充质转化中具有功能。此外,VEGFR-1 被发现通过 VEGFR-1 阳性骨髓祖细胞启动前转移龛来促进转移。据报道,VEGFR-1 通过调节免疫细胞和介导 VEGFR-1 阳性髓样细胞的免疫抑制作用,在促进炎症中发挥积极作用。鉴于 VEGFR-1 在促进血管生成、炎症、肿瘤生长和转移方面具有多功能作用,VEGFR-1 已成为治疗癌症以及与血管生成和炎症相关疾病的有前途的治疗靶点。