Jouanneau J, Moens G, Montesano R, Thiery J P
Laboratoire de Physiopathologie du Développement, URA 1337 CNRS, Ecole Normale Superieure, Paris, France.
Growth Factors. 1995;12(1):37-47. doi: 10.3109/08977199509003212.
The progressive growth of solid tumors is dependent on the tumor ability to recruit new blood vessels from the surrounding host tissues. We show here that acidic Fibroblast Growth Factor (FGF-1) produced by a rat bladder carcinoma transfected cell line (NBT-II cells) is a potent inducer of angiogenesis. After injection in nude mice, NBT-II cells transfected with FGF-1 form rapidly growing carcinomas which are highly vascularized, whereas carcinoma cells producing a biologically active form of FGF-4 behave like non-producer cells. The vasculature of the tumors obtained with NBT-II cells producing a secreted form of FGF-1 is dramatically expanded but lacking in some places a complete endothelial lining. Conditioned medium from these cells induce formation of capillary-like structures in vitro, whereas those of FGF-4 and non-secreting FGF-1 producing cells failed to induce such structures. Our results indicate that the expression of FGF-1 may promote tumor growth, at least in part, by inducing angiogenesis, and that the acquired ability of tumor cells to secrete FGF-1 but not FGF-4, may result in aberrant neovascularization of the tumor.
实体瘤的渐进性生长依赖于肿瘤从周围宿主组织募集新血管的能力。我们在此表明，大鼠膀胱癌转染细胞系（NBT-II细胞）产生的酸性成纤维细胞生长因子（FGF-1）是血管生成的有效诱导剂。在裸鼠体内注射后，转染FGF-1的NBT-II细胞形成快速生长的高度血管化的癌，而产生具有生物活性形式FGF-4的癌细胞表现得与不产生FGF-4的细胞一样。用产生分泌形式FGF-1的NBT-II细胞获得的肿瘤血管显著扩张，但在某些地方缺乏完整的内皮衬里。这些细胞的条件培养基在体外诱导形成毛细血管样结构，而FGF-4和不分泌FGF-1的细胞的条件培养基则不能诱导这种结构。我们的结果表明，FGF-1的表达可能至少部分通过诱导血管生成来促进肿瘤生长，并且肿瘤细胞获得分泌FGF-1而非FGF-4的能力可能导致肿瘤异常新生血管形成。
