Effects of epidermal growth factor (EGF) on invasive and metastatic abilities of human oral squamous cell carcinoma

In order to ascertain the effects of epidermal growth factor (EGF) on human oralsquamous cell carcinoma invasion and metastasis, we studied cell invasive and metastatic abilities by phagokinetic track assay, in vitro invasion assay, and the production of matrix-degrading enzymes by zymography of 5 human oral squamous cell carcinoma cell lines (SAS, Ca9-22, HSC-2, -3, -4). EGF (1-100ng/ml) was found to inhibit the growth of all 5 cell lines. However, phagokinetic track assay revealed that EGF enhanced the random motility of all 5 cell lines in a concentration-dependent fashion. In in vitro invasion assays, EGF increased the invasive abilities of all 5 cell lines; in particular that of SAS was significantly increased. Zymography revealed that all cell lines except for Ca9-22 produced urokinase type plasminogen activator (u-PA) and 92 kD matrix metalloproteinase (MMP-9). Exposure to EGF led to an increase in the production of u-PA and MMP-9 by the same cells. These results strongly suggest that EGF may promote human oral squamous cell carcinoma invasion and metastasis.