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We showed that anti-CD73 mAb therapy significantly delayed primary 4T1.2 and E0771 tumor growth in immune-competent mice and significantly inhibited the development of spontaneous 4T1.2 lung metastases. Notably, anti-CD73 mAb therapy was essentially dependent on the induction of adaptive anti-tumor immune responses. Knockdown of CD73 in 4T1.2 tumor cells confirmed the tumor-promoting effects of CD73. In addition to its immunosuppressive effect, CD73 enhanced tumor-cell chemotaxis, suggesting a role for CD73-derived adenosine in tumor metastasis. Accordingly, administration of adenosine-5\u2032-N-ethylcarboxamide to tumor-bearing mice significantly enhanced spontaneous 4T1.2 lung metastasis. Using selective adenosine-receptor antagonists, we showed that activation of A2B adenosine receptors promoted 4T1.2 tumor-cell chemotaxis in vitro and metastasis in vivo. In conclusion, our study identified tumor-derived CD73 as a mechanism of tumor immune escape and tumor metastasis, and it also established the proof of concept that targeted therapy against CD73 can trigger adaptive anti-tumor immunity and inhibit metastasis of breast cancer.<\/jats:p>","DOI":"10.1073\/pnas.0908801107","type":"journal-article","created":{"date-parts":[[2010,1,5]],"date-time":"2010-01-05T02:36:36Z","timestamp":1262658996000},"page":"1547-1552","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":510,"title":["Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis"],"prefix":"10.1073","volume":"107","author":[{"given":"John","family":"Stagg","sequence":"first","affiliation":[{"name":"Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Upulie","family":"Divisekera","sequence":"additional","affiliation":[{"name":"Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janelle","family":"Sharkey","sequence":"additional","affiliation":[{"name":"Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Pommey","sequence":"additional","affiliation":[{"name":"Immunology Research Centre, St. Vincent\u2019s Hospital, Melbourne 3065, Australia;"},{"name":"Department of Medicine, University of Melbourne, Melbourne 3065, Victoria, Australia; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delphine","family":"Denoyer","sequence":"additional","affiliation":[{"name":"Centre for Molecular Imaging, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen M.","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Immunology Research Centre, St. Vincent\u2019s Hospital, Melbourne 3065, Australia;"},{"name":"Department of Medicine, University of Melbourne, Melbourne 3065, Victoria, Australia; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Smyth","sequence":"additional","affiliation":[{"name":"Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[2010,1,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132715"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0402-358"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801324"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-02-136325"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0229"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2638"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.41.1.775"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605251103"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002599"},{"key":"e_1_3_3_10_2","first-page":"527","article-title":"Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review)","volume":"32","author":"Hoskin DW","year":"2008","unstructured":"DW Hoskin, JS Mader, SJ Furlong, DM Conrad, J Blay, Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review). 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