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Cancer Res. 2016 Aug 1;76(15):4372-82. doi: 10.1158/0008-5472.CAN-16-0544. Epub 2016 May 24.

Adenosine 2B Receptor Expression on Cancer Cells Promotes Metastasis.

Author information

1
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, The University of Queensland, Herston, Queensland, Australia.
2
Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Natural Sciences, Griffith University, Nathan, Queensland, Australia.
3
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
4
Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
5
Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Victoria, Australia.
6
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
7
Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier del 'Université de Montréal, Canada.
8
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, The University of Queensland, Herston, Queensland, Australia. mark.smyth@qimrberghofer.edu.au.

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.

PMID:
27221704
DOI:
10.1158/0008-5472.CAN-16-0544
[Indexed for MEDLINE]
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