Hypoxia-dependent expression of ADAM8 in human pancreatic cancer cell lines
N.V. Valkovskaya*
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology NAS of
Ukraine, Kiev, Ukraine
Abstract. 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. Aim: To
clarify the correlation between tumor hypoxia and ADAM8 protein expression. Materials and
Methods: 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. Results: 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. Conclusion: 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.
