Rde of hsulin-like grouth factor-II on tumor angiogenesis of lung cancer

众所周知，肿瘤生长依赖于新血管的发育（血管生成）。许多肿瘤细胞产生血管内皮细胞生长因子。此类生长因子包括碱性成纤维细胞生长因子（FGF）、酸性FGF、血管内皮生长因子（VEGF）和转化生长因子-α（TGF-α）。酸性FGF、碱性FGF和VEGF对肝素具有亲和力，并结合肝素琼脂糖亲和柱。我们观察到来自人肺癌细胞系T3 M-11的条件培养基对来自猪主动脉的内皮细胞具有促有丝分裂作用。该活性不与肝素琼脂糖亲和柱结合，并且在免疫学上不同于TGF-α。本研究从T3 M-11细胞制备的cDNA文库中克隆了该生长因子的cDNA，并在COS-1细胞中进行了功能性表达。该cDNA编码的核苷酸序列与胰岛素样生长因子II（IGF-II）相同。提示IGF-Ⅱ参与了恶性肿瘤细胞诱导的血管生成。

It is well recognized that tumor growth is dependent on the development of new blood vessels (angiogenesis). Many tumor cells produce growth factors of vascular endothelial cells. Such growth factors include basic fibroblast growth factor (FGF), acidic FGF, vascular endothelial growth factor (VEGF), and transforming growth factor-alpha (TGF-alpha). Acidic FGF, basic FGF and VEGF have affinity for heparin and bind to heparin sepharose affinity columns. We observed that the conditioned medium from a human lung cancer cell line T3M-11 was mitogenic for endothelial cells derived from porcine aorta. The activity did not bind to a heparin sepharose affinity column and was different from TGF-alpha immunologically. These findings led us to analyze the growth factor produced by T3M-11 cells.A cDNA encoding the growth factor was isolated through functional expression cloning in COS-1 cells from a cDNA library prepared from T3M-11 cells. The nucleotide sequence encoded by the cDNA proved to be identical with insulin-like growth factor II (IGF-II). The result suggests the involvement of IGF-II in the angiogenesis induced by the malignant tumor cells.