Laparoscopic surgery protects against the oncologic adverse effects of open surgery by attenuating endothelial progenitor cell mobilization

Abstract

Endothelial progenitor cells (EPCs) derived from bone marrow incorporate into foci of neovascularization to propagate tumor growth. These cells are mobilized in response to surgical injury. Laparoscopic surgery may protect against the oncologic adverse effects of open surgical tumor excision, and this may be related to attenuated mobilization of EPCs. For this study, 132 C57BL/6 mice were randomized to standardized laparotomy, laparoscopy, or control groups. The animals were killed at 6, 24, 48, and 72 h. Femur bone marrow and peripheral blood were harvested. Bone marrow EPCs were detected by flow cytometric dual staining for the stem cell antigen-1/cKit phenotype. Circulating EPCs were characterized in blood by vascular endothelial growth factor receptor 2 positive/macrophage activating complement-1 negative staining. Separately, 12 C57/bl6 mice bearing 3LL Lewis lung tumors 12 days after laparotomy or laparoscopy had their tumors excised and examined for endothelial cell expression (marker P1H12). Laparoscopy decreased circulating EPCs and bone-marrow EPC levels, as compared with laparotomy, at all time points. Bone marrow EPC levels were 2.95% +/- 0.32% after laparotomy, as compared with 0.65 +/- 0.21 in the laparoscopy group (p < 0.05). The circulating EPC level in the laparotomy group was 35.2% +/- 6% of cells, as compared with 3.1% +/- 0.2% in the laparoscopy group (p < 0.05). In homogenized tumors, the percentage of P1H12 expression among laparoscopy-treated animals was 22.1% +/- 4.2%, as compared with 39% +/- 8% in the laparotomy group (p < 0.05). Laparoscopy decreased EPC levels in both bone marrow and circulation, resulting in decreased tumor endothelial cell burden. This may represent a novel mechanism by which laparoscopy protects against the oncologic adverse effects of open surgical tumor excision.