Abstract:

Background and purpose: In recent years, the studies indicated that postoperatively induced myeloid-derived suppressor cells (MDSCs) were qualified with potent proangiogenic and tumor-promotive ability. Bone marrow mesenchymal stem cells (BMSCs) significantly inhibited the induction and proliferation of MDSCs. However, the relationship of MDSCs and tumor metastasis during perioperative period, and whether BMSCs could prevent tumor metastasis through inhibiting MDSCs are not clarified. This study aimed to investigate the change of MDSCs during perioperative period and its correlation with tumor metastasis after surgery, and the influence of BMSCs on the induction of MDSCs and the development of postoperative tumor metastasis. Methods: LLC cells were injected intravenously into C57BL/6 mice. Two hours later, these mice were divided into 4 groups: controls (C group); mice given anesthesia (A group); mice given anesthesia and laparotomy (AL group) and mice given anesthesia, laparotomy, and hepatic lobectomy (ALH group). The AL mice were divided into 2 groups after surgical operation: the AL mice without treatment (ALL group) and the AL mice treated with syngeneic BMSCs (ALB group). The percentage of Gr- 1⁺CD11b⁺ cells in peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. The numbers of metastases on the lung surface were counted on the 14^th day after LLC infusion. BMSCs were also co-cultured in vitro with myeloid cells in order to illustrate the effects of BMSCs on the generation of MDSCs. Results: The numbers of lung metastases in AL and ALH group significantly increased as compared with C and A group (P<0.01). The number of lung metastases in ALH group significantly increased as compared with AL group (P<0.05). The percentage of Gr-1⁺CD11b⁺ cells in PBMCs during postoperative period significantly increased in AL and ALH group as compared with C and A group, and the percentage of Gr-1⁺CD11b⁺ cells in ALH group also significantly increased as compared with AL group. The numbers of lung metastases in AL and ALB group were (38.00±9.57) and (6.54±1.49), the difference was statistically significant (P<0.01) on day 14 after LLC infusion. Meanwhile, the percentage of Gr-1⁺CD11b⁺ cells in ALB group significantly decreased as compared with AL1 group. This study also demonstrated that BMSCs inhibited the induction and proliferation of MDSCs from myeloid cells in vitro. Conclusion: Surgery stress induces MDSCs and promotes tumor metastasis. Syngeneic BMSCs could inhibit the generation of MDSCs and further suppress tumor metastasis after surgery.

Key words: Mesenchymal stem cell, Myeloid cells, Postoperative period, Neoplasm metastasis