Abstract
Background
Endothelial progenitor cells (EPCs) derived from bone marrow incorporate into foci of neovascularization to propogate 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.
Methods
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).
Results
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).
Conclusion
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.
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References
Condon ET, Wang JH, Redmond HP (2004) Surgical injury induces the mobilization of endothelial progenitor cells. Surgery 135: 657–661
Da Costa ML, Redmond HP, Bouchier-Hayes DJ (1998) The effect of laparotomy and laparoscopy on the establishment of spontaneous tumor metastases. Surgery 124: 516–525
Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, et al. (2001) Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res 88: 167–174
Harmey JH, Bucana CD, Lu W, Byrne AM, M’Donnell S, et al. (2002) Lipopolysaccharide-induced metastatic growth is associated with increased angiogenesis, vascular permeability, and tumor cell invasion. Int J Cancer 101: 415–422
Harmon GD, Senagore AJ, Kilbride MJ, Warzynski MJ (1994) Interleukin-6 response to laparoscopic and open colectomy. Dis Colon Rectum 37: 754–759
Jacobi CA, Bonjer HJ, Puttick MI, O’Sullivan R, Lee SW, et al. (2002) Oncologic implications of laparoscopic and open surgery. Surg Endosc 16: 441–445
Lacey AM, Garcia-Valdecasas JC, Delgado S, Castells A, et al. (2002) Laparoscopy-assisted colectomy versus open colectomy for treatment of nonmetastatic colon cancer: a randomised trial. Lancet 359: 2224–2229
Lyden D, Hattori K, Dias S, Costa C, Blaikie P, et al. (2001) Impaired recruitment of bone marrow–derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 11: 1194–1201
Mancuso P, Burlini A, Pruneri G, Goldhimsch A, Nartinelli G, et al. (2001) Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood 97: 3658–3661
Mutter D, Hajri A, Tassetti V, Solis-Caraj C, Aprahamian M, et al. (1996) Experimental pancreatic tumor growth and spread after laparoscopy versus laparotomy in the rat. Surg Endosc 10: 566
Peters BA, Diaz LA, Polyak K, Meszler L, Romans K, et al. (2005) Contribution of bone marrow–derived endothelial cells to human tumor vasculature. Nat Med 11: 261–262
St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, et al. (2000) Genes expressed in human tumor endothelium. Science 289: 1197–1202
Wang E, Ngalame Y, Panelli MC, Nguyen-Jackson H, Deavers M, et al. (2005) Peritoneal and subperitoneal stroma may facilitate regional spread of ovarian cancer. Clin Cancer Res 11: 113–122
Watson RW, Redmond HP, McCarthy J, Londron L, Bouchier-Hayes D, et al. (1995) Exposure of the peritoneal cavity to air regulates early inflammatory responses to surgery in a murine model. Br J Surg 82: 1060–1065
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Condon, E.T., Barry, B.D., Wang, J.H. et al. Laparoscopic surgery protects against the oncologic adverse effects of open surgery by attenuating endothelial progenitor cell mobilization. Surg Endosc 21, 87–90 (2007). https://doi.org/10.1007/s00464-005-0701-9
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DOI: https://doi.org/10.1007/s00464-005-0701-9