Adenosine 2B Receptor Expression on Cancer Cells Promotes Metastasis.

Abstract

Adenosine plays an important role in inflammation and tumor development, progression, and responses to therapy. We show that an adenosine 2B receptor inhibitor (A2BRi) decreases both experimental and spontaneous metastasis and combines with chemotherapy or immune checkpoint inhibitors in mouse models of melanoma and triple-negative breast cancer (TNBC) metastasis. Decreased metastasis upon A2BR inhibition is independent of host A2BR and lymphocytes and myeloid cells. Knockdown of A2BR on mouse and human cancer cells reduces their metastasis in vivo and decreases their viability and colony-forming ability, while transiently delaying cell-cycle arrest in vitro The prometastatic activity of adenosine is partly tumor A2BR dependent and independent of host A2BR expression. In humans, TNBC cell lines express higher A2BR than luminal and Her2(+) breast cancer cell lines, and high expression of A2BR is associated with worse prognosis in TNBC. Collectively, high A2BR on mouse and human tumors promotes cancer metastasis and is an ideal candidate for therapeutic intervention. Cancer Res; 76(15); 4372-82. ©2016 AACR.

• Authors: Deepak Mittal, Debottam Sinha, Deborah Barkauskas, Arabella Young, Murugan Kalimutho, Kimberley Stannard, Franco Caramia, Benjamin Haibe-Kains, John Stagg, Kum Kum Khanna, Sherene Loi, Mark J Smyth
• Journal: Cancer research (Cancer Res) Vol. 76 Issue 15 Pg. 4372-82 (08 01 2016) ISSN: 1538-7445 [Electronic] United States
• PMID: 27221704 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Receptor, Adenosine A2B

Topics

• Animals
• Cell Line, Tumor
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Neoplasm Metastasis
• Receptor, Adenosine A2B (metabolism)
• Signal Transduction