Keratinocyte growth factor induces vascular endothelial growth factor-A expression in colorectal cancer cells
Keratinocyte growth factor induces vascular endothelial growth factor-A expression in colorectal cancer cells
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DOI：
10.3892/ijo_00000158
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发表时间：
2009-02-01
影响因子：
5.2
通讯作者：
Naito, Zenya
中科院分区：
文献类型：
--
作者：
Narita, Kosuke;Fujii, Takenori;Naito, Zenya
角质形成细胞生长因子（keratinocytegrowthfactor，KGF）又称成纤维细胞生长因子（fibroblastgrowthfactor，FGF）-7，属于FGF家族。KGF通常不由人类癌细胞产生，但KGF受体（KGFR）在大多数癌细胞中表达，并且在分化良好的癌症类型中特别高表达。近年来，有研究表明KGF可诱导胰腺癌细胞表达血管内皮生长因子（VEGF）-A。VEGF-A由某些癌细胞产生，在包括结肠直肠癌细胞在内的癌细胞的血管生成和转移中起重要作用。在这项研究中，我们研究了重组人KGF（rhKGF）是否诱导主要的血管生成生长因子，包括VEGF-A，FGF-2和肝细胞生长因子（HGF）在人结直肠癌细胞（HCT-15），表达高水平的KGFR，但低或可忽略不计的KGF水平。rhKGF可显著提高HCT-15细胞无血清培养液中VEGF-A的表达水平，但FGF-2和HGF的表达水平较低，无法检测到。此外，在通过KGF基因转染诱导稳定过表达KGF的KGF转染HCT-15细胞和模拟转染细胞（Mock）中评价血管生成生长因子的表达水平。转染KGF的HCT-15细胞中KGF和VEGF-A的表达水平以及无血清培养液中的蛋白浓度均显著高于Mock细胞。相比之下，FGF-2和HGF mRNA表达水平在转染KGF的HCT-15细胞和Mock细胞之间没有显著差异，并且细胞的无渣培养基中的蛋白质浓度低于检测水平。这些发现表明，rhKGF和内源性KGF基因在结直肠癌细胞中的过度表达增加了VEGF-A的产生，并可能与癌症中的血管生成有关。
Keratinocyte growth factor (KGF), which is also called fibroblast growth factor (FGF)-7, belongs to the FGF family. KGF is not commonly produced by human cancer cells, but the KGF receptor (KGFR) is expressed in most cancer cells and particularly highly expressed in well-differentiated types of cancer. Recently, it has been reported that vascular endothelial growth factor (VEGF)-A expression is induced by KGF in pancreatic cancer cells. VEGF-A is produced by some cancer cells and plays important roles in the angiogenesis and metastasis of cancer cells including those in the colorectum. In this study, we examined whether recombinant human KGF (rhKGF) induces major angiogenic growth factors including VEGF-A, FGF-2 and hepatocyte growth factor (HGF) in human colorectal cancer cells (HCT-15), which express a high level of KGFR, but a low or negligible level of KGF. rhKGF significantly increased the VEGF-A expression level in a serum-free medium of HCT-15 cells, but FGF-2 and HGF expression levels were too low to detect. Furthermore, the expression levels of the angiogenic growth factors were evaluated in KGF-transfected HCT-15 cells, which were induced to stably overexpress KGF by KGF gene transfection and mock-transfected cells (Mock). KGF and VEGF-A expression levels in the cells and the protein concentrations in serum-free medium were significantly higher in KGF-transfected HCT-15 cells than in Mock cells. In contrast, the FGF-2 and HGF mRNA expression levels were not significantly different between KGF-transfected HCT-15 cells and Mock cells and the protein concentrations in scrum-free medium of the cells were below the detection level. These findings suggest that administration of rhKGF and over-expression of endogenous KGF genes in colorectal cancer cells increase VEGF-A production and may relate to angiogenesis in cancer.