title: 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.affiliation: Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, The University of Queensland, Herston, Queensland, Australia.
authors.forename: Deepak
authors.initials: D
authors.lastname: Mittal
authors.affiliation: Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Natural Sciences, Griffith University, Nathan, Queensland, Australia.
authors.forename: Debottam
authors.initials: D
authors.lastname: Sinha
authors.affiliation: Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Deborah
authors.initials: D
authors.lastname: Barkauskas
authors.affiliation: Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, The University of Queensland, Herston, Queensland, Australia.
authors.forename: Arabella
authors.initials: A
authors.lastname: Young
authors.affiliation: Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Murugan
authors.initials: M
authors.lastname: Kalimutho
authors.affiliation: Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Stannard
authors.affiliation: Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Victoria, Australia.
authors.forename: Franco
authors.initials: F
authors.lastname: Caramia
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haibe-Kains
authors.affiliation: Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier del 'Université de Montréal, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Stagg
authors.affiliation: Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Kum Kum
authors.initials: KK
authors.lastname: Khanna
authors.affiliation: Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Victoria, Australia.
authors.forename: Sherene
authors.initials: S
authors.lastname: Loi
authors.affiliation: 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.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D043704:Receptor, Adenosine A2B