Effects of EGF and TGF-alpha on invasion and proteinase expression of uterine cervical adenocarcinoma OMC-4 cells.

M Ueda, H Fujii, K Yoshizawa, Y Terai, K Kumagai, K Ueki, M Ueki
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引用次数: 24

Abstract

Uterine cervical adenocarcinoma typically is an aggressive neoplasm with a propensity for early invasion and dissemination; however, the regulatory mechanism of invasive activity of cervical adenocarcinoma cells has not been fully understood. In this study, biological effects of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha on invasion and proteinase expression of human cervical adenocarcinoma OMC-4 cells were investigated. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into the reconstituted basement membrane were stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. Their effects on tumor cell migration were also confirmed by wound assay. The zymography of tumor-conditioned medium showed that the treatment of OMC-4 cells with EGF and TGF-alpha resulted in the increase of matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (uPA). Matrilysin (MMP-7), also secreted by OMC-4 cells, was not affected by these growth factors. These results suggest that EGF and TGF-alpha act as positive regulators on the invasion of cervical adenocarcinoma cells, which may be associated with their stimulatory effects on tumor cell motility and the induction of type IV collagenase and uPA secreted by tumor cells.

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EGF和tgf - α对子宫颈腺癌OMC-4细胞侵袭及蛋白酶表达的影响
子宫颈腺癌是一种典型的侵袭性肿瘤,具有早期侵袭和传播的倾向;然而,对宫颈腺癌细胞侵袭性的调控机制尚不完全清楚。本研究探讨了表皮生长因子(EGF)和转化生长因子(TGF)- α对人宫颈腺癌OMC-4细胞侵袭及蛋白酶表达的生物学效应。0.1-10 nM的EGF和tgf - α刺激肿瘤细胞沿基质结合的纤维连接蛋白梯度迁移,并以浓度依赖的方式侵入重建的基底膜。伤口实验也证实了它们对肿瘤细胞迁移的影响。肿瘤条件培养基酶谱分析显示,EGF和tgf - α处理OMC-4细胞可导致基质金属蛋白酶(MMP)-2和尿激酶型纤溶酶原激活物(uPA)的升高。同样由OMC-4细胞分泌的基质溶素(MMP-7)不受这些生长因子的影响。上述结果提示,EGF和tgf - α在宫颈腺癌细胞的侵袭过程中发挥正向调节作用,这可能与其刺激肿瘤细胞运动、诱导肿瘤细胞分泌IV型胶原酶和uPA有关。
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