Hypoxia-dependent expression of ADAM8 in human pancreatic cancer cell lines

Exp Oncol. 2008 Jun;30(2):129-32.

Abstract

Background: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / biosynthesis*
  • Cell Hypoxia
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypoxia*
  • Immunoblotting
  • Membrane Proteins / biosynthesis*
  • Neoplasm Invasiveness
  • Oxygen / chemistry
  • Pancreatic Neoplasms / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Membrane Proteins
  • RNA, Messenger
  • ADAM Proteins
  • ADAM8 protein, human
  • Oxygen