Hypoxia Inducible Adenosine A2B Receptor Modulates Proliferation of Colon Carcinoma Cells
D Ma, T Kondo, T Nakazawa, D Niu, T Kawasaki, K Mochizuki, T Yamane, R Katoh. University of Yamanashi, Chuo, Yamanashi, Japan
Background: Extracellular adenosine regulates a wide variety of physiological processes interacting with four adenosine receptor-A1, -A2A, -A2B, and -A3 subtypes. However, little is known of their pathophysiological roles in human cancers.
Design: In this study, we examined the expression pattern of adenosine receptors in various colorectal tissues (nomal colon mucosa, tubular adenomas, and tubular adenocarcinomas) and human colon carcinoma cell lines (DLD-1, SW480, HCT-15, LOVO, and COLO205). Moreover, we studied the effect of selective antagonist against adenosine receptors on cancer cell proliferation.
Results: Using RT-PCR and Western blotting, we found that adenosine receptor A2B (ADORA2B) was consistently upregulated in colorectal carcinoma tissues and colon cancer cell lines compared with normal colorectal mucosa. In immunohistochemistry, diffuse immunopositivity of ADORA2B was observed in 64% of colorectal adenocarcinomas (27/42), while 15% in tubular adenomas (3/20) and 0% in normal colon glands (0/62). We also found significant induction of ADORA2B expression by hypoxia state in mRNA level at 8 hour incubation and in protein level at 24 hour incubation in colon carcinoma cell lines. To examine the function of ADORA2B, we applied ADORA2B selective antagonist (MRS1754) in colon carcinoma cells. Then, significant growth inhibitory effect of MRS1754 was demonstrated with dose-dependent manner by MTT cell proliferation assay.
Conclusions: In conclusion, ADORA2B was overexpressed in colon carcinomas relevant with hypoxic state, presumably promoting cancer cell growth. Our date suggested adenosine receptor is a potential therapeutic target for colorectal cancer.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 127, Tuesday Morning