Disintegrin and metalloproteinase domain-containing protein 8
cellular response to hypoxia
Hypoxia-dependent expression of ADAM8 in human pancreatic cancer cell lines.
<h4>Background</h4>One of the most characteristic features of malignant tissue is the high level of intratumoral hypoxia, which is considered as a powerful factor for induction of tumor aggressiveness and malignant progression. Pancreatic cancer (PC) is a near fatal disease with very unfavorable clinical outcome despite the application of different treatment regimes. It was shown that PC is characterized by high level of hypoxia.<h4>Aim</h4>To clarify the correlation between tumor hypoxia and ADAM8 protein expression.<h4>Materials and methods</h4>ASPC-1, Panc-1, BxPC-3, Capan-1, MiaPaCa-2, Colo-357, Su8686 and T3M4 cell lines were used in the study. Expression of mRNA ADAM8 was evaluated by real-time quantitative polymerase chain reaction method. Immunoblot analysis was used to evaluate the expression of ADAM8 protein.<h4>Results</h4>Hypoxia induced a 2.5-5.9-fold increase of ADAM8 mRNA levels of in the examined pancreatic cancer cell lines except Panc-1 (p=0.046). On the protein level, hypoxia induced a 1.2-5.9-fold increase of the ADAM8 prodomain removal form (90 kDa) in 5/8 pancreatic cancer cells. Moreover, hypoxia induced a 1.3-2.0-fold increase of the remnant form ADAM8 (60 kDa) in 4/8 pancreatic cancer cell lines: Aspc-1, Colo-357, Panc-1, T3M4.<h4>Conclusion</h4>It was observed the clear tendency in the increase both of ADAM8 mRNA and ADAM8 protein levels in pancreatic cancer cell lines under hypoxia compared to normal conditions of oxygenation. A potential role of ADAM8 as a hypoxia-dependent protein in the pathogenesis and evolution of pancreatic cancer that is characterized by high level of intratumoral hypoxia can be suggested.