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.


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.


CONCLUSIONS
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.
Zelvyte
Inga
I
Department of Medicine, University Hospital Malmö, S-20502, Malmö, Sweden.
Ohlsson
Bodil
B
Axelson
Jan
J
Janciauskiene
Sabina
S
D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D016328:NF-kappa B / Q000096:biosynthesis; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
D016207:Cytokines; D015850:Interleukin-6; D016328:NF-kappa B; D010446:Peptide Fragments; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D000515:alpha 1-Antitrypsin