Details

Autor(en) / Beteiligte

• Liu, Xuan-Hui
• Wu, Xian-Rui
• Lan, Nan
• Zheng, Xiao-Bin
• Zhou, Chi
• Hu, Tuo
• Chen, Yu-Feng
• Cai, Ze-Rong
• Chen, Ze-Xian
• Lan, Ping
• Wu, Xiao-Han

Titel

CD73 promotes colitis‑associated tumorigenesis in mice

Ist Teil von

• Oncology letters, 2020-08, Vol.20 (2), p.1221-1230

Ort / Verlag

Athens: Spandidos Publications

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Patients with inflammatory bowel disease (IBD) are at a higher risk of developing colitis-associated colorectal cancer. The aim of the present study was to investigate the role of CD73 in IBD-associated tumorigenesis. A mouse model of colitis-associated tumorigenesis (CAT) induced by azoxymethane and dextran sulfate sodium was successfully constructed. Model mice were injected with CD73 inhibitor or adenosine receptor agonist. Colon length, body weight loss and tumor formation were assessed macroscopically. Inflammatory cytokine measurement and RNA sequencing on colon tissues were performed. Inhibition of CD73 by adenosine 5'-([alpha],[beta]-methylene) diphosphate (APCP) suppressed the severity of CAT with attenuated weight loss, longer colons, lower tumor number and smaller tumor size compared with the model group. Activation of adenosine receptors using l-(6-amino-9H-purin-9-yl)-l-deoxy-N-ethyl-[beta]-D-ribofuranur onamide (NECA) exacerbated CAT. Histological assessment indicated that inhibition of CD73 reduced, while activation of adenosine receptors exacerbated, the histological damage of the colon. Increased expression of pro-inflammatory cytokines (tumor necrosis factor-[alpha] and interleukin-6) in colonic tissue was detected in the NECA group. According to RNA sequencing results, potential oncogenes such as arachidonate 15-lipoxygenase (ALOX15), Bcl-2-like protein 15 (Bcl2115) and N-acetylaspartate synthetase (Nat81) were downregulated in the APCP group and upregulated in the NECA group compared with the model group. Therefore, inhibition of CD73 attenuated IBD-associated tumorigenesis, while activation of adenosine receptors exacerbated tumorigenesis in a C57BL/6J mouse model. This effect may be associated with the expression of pro-inflammatory cytokines and the regulation of ALOX15, Bcl2115 and Nat81.