The influence of myeloid derived suppressor cells on angiogenesis and tumor growth after cancer surgery

Abstract

While myeloid-derived suppressor cells (MDSCs) have been reported to participate in the promotion of angiogenesis and tumor growth, little is known about their presence and function during peri-operative period. Here, we demonstrated that human MDSCs expressing CD11b⁺, CD33⁺ and HLA-DR^– significantly increased in lung cancer patients after thoractomy. CD11b⁺CD33⁺HLA-DR^– MDSCs isolated 24 hours after surgery from lung cancer patients were more efficient in promoting angiogenesis and tumor growth than MDSCs isolated before surgical operation in allograft tumor model. In addition, CD11b⁺CD33⁺HLA-DR^– MDSCs produced high levels of MMP-9. Using an experimental lung metastasis mouse model, we demonstrated that the numbers of metastases on lung surface and Gr-1⁺CD11b⁺ MDSCs at post-operative period were enhanced in proportion to the degree of surgical manipulation. We also examined that syngeneic bone marrow mesenchymal stem cells (BMSCs) significantly inhibited the induction and proliferation of Gr-1⁺CD11b⁺ MDSCs and further prevented lung metastasis formation in the mice undergoing laparotomy. Taken together, our results suggest that post-operatively induced MDSCs were qualified with potent pro-angiogenic and tumor promotive ability and this cell population should be considered as a target for preventing post-operative tumor metastasis. This article is protected by copyright. All rights reserved.

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