Abstract 5192: The mobilization and recruitment of bone marrow-derived stem cells contributes to the acceleration of tumor growth after surgery

Abstract

Abstract Background. Although surgical resection of the primary tumor lesion is still the most promising strategy for cancer therapy, surgical injury may accelerate tumor growth and metastasis, negatively affecting patients’ prognosis. Previous studies have demonstrated that many factors, including the robust release of cytokines and temporal changes of immunological and inflammatory mediators may contribute to the acceleration of tumor growth and metastasis after surgery. However, the precise mechanisms are not yet fully understood. We tested the hypothesis that surgical injury induces mobilization and recruitment of bone marrow-derived stem cells, thereby enhancing angiogenesis and accelerating tumor growth. Methods. Mice were subjected to partial gastrectomy, and non-gastrectomized mice were used as controls. Mobilization of bone marrow stem cells was monitored after surgery. Using an established tumor model in GFP+ bone marrow-transplanted chimera mice, we further investigated whether the mobilized stem cells affected tumor growth. To evaluate the influence on tumor growth of surgical injury and the inhibition of SDF-1/CXCR4 signals, we used AMD3100, a CXCR4 antagonist. Results. Compared to control, gastrectomy significantly increased the populations of CD34+ cells (6.9±4.5% vs 3.3±0.4%, p<0.05) and CD34+/Flk-1+ cells (0.08±0.02% vs 0.05±0.01%, p<0.05) in peripheral blood 12 hours after surgery. Twelve days after surgery, the tumor volume was almost double in gastrectomized mice compared with control (580±106 mm3 vs 299±162 mm3, p<0.05). Histological analysis of tumor tissue revealed that the microvessel density and number of proliferating cells were significantly higher, but those of apoptotic cells were significantly lower, in gastrectomized mice as compared with control. Furthermore, the number of GFP+ cells found in tumor tissue was significantly larger in mice that underwent gastrectomy than in control. Some of the stained GFP+ cells were positive for CD34 and had been incorporated into microvessels. However, administration of AMD3100 significantly inhibited the recruitment of GFP+ cells and completely negated the acceleration in tumor growth after surgery (345±172 mm3, p<0.05). Conclusion. Surgical injury induces mobilization and recruitment of bone marrow stem cells, thereby enhancing angiogenesis and accelerating tumor growth. Temporary inhibition of the SDF-1/CXCR4 signals may represent new therapeutic strategies for preventing acceleration of tumor growth after surgery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5192. doi:10.1158/1538-7445.AM2011-5192