Diverse responses between human pancreatic cancer cell lines to native alpha 1-antitrypsin and its C-terminal fragment.

BACKGROUND: Previous studies imply that human pancreatic cancer cells have a wide heterogeneity and their exposure to various agents may give unpredictable results in clinical situations. MATERIALS AND METHODS: The cell lines LPC-3, -5 and -10, established from primary cultures of pancreatic adenocarcinoma, were exposed to 5 microM of AAT or its C-terminal peptide C-36 for 24 hours and analysed for cytokines by an enzyme-linked immunosorbent assay and for NF kappa B by the electrophoretic mobility shift assay. RESULTS: Native AAT lowers TGF-beta 1 levels and increases NF-kappa B activity in LPC-3 cells, while C-36 increases TGF-beta 1 levels and up-regulates NF-kappa B in LPC-5 cells. In LPC-10 cells AAT lowers TGF-beta 1. However, both AAT and C-36 fail to cause a change in NF-kappa B expression. For LPC-10 cells treated with C-36 IL-6 and TNF-alpha levels also increase. CONCLUSION: Our findings provide evidence that human cancer cell lines originating from primary pancreatic tumors do not have a uniform response to the same stimulus which shows a great heterogenicity among pancreatic cancer cells. Serine proteinase inhibitor, AAT, dependent on its molecular form, is also found to exert diverse effects on the properties of tumour cells confirming the complexity of cell-protein interaction.