Jayson G C, Evans G S, Pemberton P W, Lobley R W, Allen T
Department of Medical Oncology, Paterson Institute for Cancer Research, Withington, Manchester, United Kingdom.
Cancer Res. 1994 Nov 1;54(21):5718-23.
Basic fibroblast growth factor (bFGF) is found in the extracellular matrix and around the endothelial and epithelial cells of some human colon carcinomas. It is believed to play a role in angiogenesis, but in addition, recent data suggest that it can directly stimulate mitogenesis in some colon carcinoma cell lines. To clarify the role of bFGF in human colon carcinoma, we developed a model of Caco-2 which grew in serum-free conditions so that the effect of bFGF on multiplication, migration, and differentiation could be studied in defined conditions. Through morphological and biochemical studies in serum-free conditions, we demonstrated that this subline of Caco-2 differentiated spontaneously on reaching confluence. Using this model, we found that bFGF did not affect differentiation but that multiplication and migration were increased. The implication of these findings is that bFGF, released from the extracellular matrix by invading cells or produced by neovascular endothelial cells, can increase the mitogenic rate and migratory potential of colon carcinoma cells. In addition, the dual role of bFGF in stimulating colon carcinoma cells directly and promoting angiogenesis suggests that anti-bFGF strategies could form the basis of a novel approach to the treatment of colon carcinoma.
碱性成纤维细胞生长因子(bFGF)存在于细胞外基质以及一些人类结肠癌的内皮细胞和上皮细胞周围。人们认为它在血管生成中起作用,但此外,最近的数据表明它可以直接刺激某些结肠癌细胞系的有丝分裂。为了阐明bFGF在人类结肠癌中的作用,我们建立了一个在无血清条件下生长的Caco-2模型,以便在特定条件下研究bFGF对增殖、迁移和分化的影响。通过在无血清条件下的形态学和生化研究,我们证明了Caco-2的这个亚系在达到汇合状态时会自发分化。利用这个模型,我们发现bFGF不影响分化,但会增加增殖和迁移。这些发现的意义在于,由侵袭细胞从细胞外基质释放或由新生血管内皮细胞产生的bFGF,可以提高结肠癌细胞的有丝分裂率和迁移潜能。此外,bFGF在直接刺激结肠癌细胞和促进血管生成方面的双重作用表明,抗bFGF策略可能构成一种治疗结肠癌新方法的基础。