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


OBJECTIVE
To clarify the correlation between tumor hypoxia and ADAM8 protein expression.


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.


CONCLUSIONS
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.
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology NAS of Ukraine, Kiev, Ukraine. osion@onconet.kiev.ua
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Valkovskaya
D051722:ADAM Proteins / Q000096:biosynthesis*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D015151:Immunoblotting; D008565:Membrane Proteins / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D010100:Oxygen / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008565:Membrane Proteins; D012333:RNA, Messenger; D051722:ADAM Proteins; C068490:ADAM8 protein, human; D010100:Oxygen