The response to epidermal growth factor of human maxillary tumor cells in terms of tumor growth, invasion and expression of proteinase inhibitors

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Abstract
Three cancer cell lines, IMC‐2, IMC‐3 and IMC‐4, were established from a single tumor of a patient with maxillary cancer. We examined responses to epidermal growth factor (EGF) of these 3 cell lines with regard to cell growth and tumor invasion. The growth rate of IMC‐2 in nude mice was markedly faster than that of the IMC‐3 and IMC‐4 cell lines. Assay for invasion through fibrin gels showed significantly enhanced invasive capacity of IMC‐2 cells in response to EGF, but no change for IMC‐3 and IMC‐4 cells. We examined response to EGF of IMC‐2 cells with regard to expression of a growth‐related oncogene (c‐fos), proteinases and their inhibiton. Expression of c‐fos was transiently increased in IMC‐2 cells at rates comparable to those seen in the 2 other lines in the presence of EGF. There was no apparent effect of EGF on the expression of urokinase‐type plasminogen activator and 72‐kDa type‐IV colla‐genase in IMC‐2 cells. In contrast, EGF specifically enhanced the expression of plasminogen activator inhibitor‐I (PAI‐1) and tissue inhibitor of metalloproteinases‐1 (TIMP‐1) in IMC‐2 cells. Our data suggest that proteinase inhibitors or other related factors may play an important role in tumor growth and invasion in response to EGF.

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