Combined interferon-gamma and tumor necrosis factor-alpha treatment differentially affects adhesion and migration of keratinocyte-derived cells to laminin-1

Interactions with the extracellular matrix constitute basic steps in cervix carcinoma cell invasion. In this study, we examined the adhesion and migra tion profiles of two human papillomavirus (HPV) DNA-transfected keratinocyt e-derived cell lines, EIL8 and 18-1 1S3, and of the cervix adenocarcinoma S iHa cell line, towards laminin-1, and the selective effect of a 24-72h trea tment of 1000 U/ml interferon-gamma (IFN-gamma) and tumor necrosis factor-a lpha(TNF-alpha), a treatment that significantly decreases cervix carcinoma cell proliferation and progression in nude mice, on these parameters. Compa red to normal cervix keratinocytes (CK) and two HPV DNA-transfected keratin ocyte cell lines, in basal conditions, the SiHa cell line was characterized by increased attachment (SiHa, 48.74 +/- 4.02 vs. normal keratinocytes, 4. 32 +/- 0.40, EIL8, 17.80 +/- 3.03 and 18-1 1S3, 17.82 +/- 1.48% of attached cells after 30 min) and marked directed chemotactic migration towards lami nin-1. Interestingly, treatment of the cells with the cytokines (1000 U/ml IFN-gamma and TNF-ol) did not modulate the adhesion properties of the cells , but chemotactic migration of SiHa cells to laminin-1 was significantly de creased, while migration towards type I collagen was increased. Similar res ults were obtained with the Ca Ski cervix carcinoma cell line. Our results emphasize the altered pattern of interactions of cervix carcinoma cells wit h extracellular matrix components such as laminin-1, compared to normal and preneoplastic cells, and contributes to the understanding of the effects o f cytokine treatment on cervix carcinoma cells.