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

众所周知，肿瘤的生长依赖于新血管的发展(血管生成)。许多肿瘤细胞产生血管内皮细胞生长因子。这些生长因子包括碱性成纤维细胞生长因子、酸性成纤维细胞生长因子、血管内皮生长因子和转化生长因子-α。酸性成纤维细胞生长因子、碱性成纤维细胞生长因子和血管内皮生长因子对肝素具有亲和力，并与肝素琼脂糖亲和柱结合。我们观察到人肺癌细胞系T3M-11的条件培养液对猪主动脉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，在免疫学上不同于转化生长因子-α。这些发现促使我们对T3M-11细胞产生的生长因子进行了分析。通过在COS-1细胞中进行功能表达克隆，从T3M-11细胞的cDNA文库中分离到了编码该生长因子的基因。该基因编码的核苷酸序列与胰岛素样生长因子II(IGF-II)完全一致。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.