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

Int J Cancer. 2016 Jun 1;138(11):2688-99. doi: 10.1002/ijc.29998. Epub 2016 Jan 25.


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 perioperative period. Here, we demonstrated that human MDSCs expressing CD11b(+), CD33(+) and HLA-DR(-) significantly increased in lung cancer patients after thoracotomy. CD11b(+) CD33(+) HLA-DR(-) MDSCs isolated 24 hr 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 postoperative 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 postoperatively induced MDSCs were qualified with potent proangiogenic and tumor-promotive ability and this cell population should be considered as a target for preventing postoperative tumor metastasis.

Keywords: bone marrow mesenchymal stem cells; lung cancer; metastasis; myeloid-derived suppressor cells; perioperative period.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11b Antigen / genetics
  • Cell Proliferation / genetics*
  • Flow Cytometry
  • HLA-DR Antigens / genetics
  • Humans
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Lung Neoplasms / therapy*
  • Matrix Metalloproteinase 9 / biosynthesis
  • Mice
  • Myeloid Cells / transplantation*
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / therapy*
  • Sialic Acid Binding Ig-like Lectin 3 / genetics
  • Xenograft Model Antitumor Assays


  • CD11b Antigen
  • CD33 protein, human
  • HLA-DR Antigens
  • ITGAM protein, human
  • Sialic Acid Binding Ig-like Lectin 3
  • Matrix Metalloproteinase 9