Abstract
The use of laparoscopic techniques for curative resections of malignant tumours has been under scrutiny. The potential benefits to the patient in the form of earlier recovery and less immune paresis are countered by the reports of increased tumour recurrence. The biological sequelae of the hypoxic laparoscopic environment on tumour cells is unknown. Components of the metastatic cascade were evaluated under in vitro laparoscopic conditions using a human colonic adenocarcinoma cell line (SW1222). Exposure to the laparoscopic gases carbon dioxide and helium for 4 h, comparable to the duration of a laparoscopic colorectal resection, had no effect on cell viability. A cellular hypoxic insult was demonstrated by the induction of hypoxia inducible factor 1α (HIF-1α). Exposure also resulted in significant reduction in homotypic adhesion as well as to a variety of extracellular matrix components. These effects were recoverable under re-oxygenation. The changes were reflected at the molecular level by significant down regulation of adhesion molecules known to be involved in tumour progression (E-cadherin, CD44 and β1 sub-unit). Modulation of adherence has significant implications for laparoscopic oncological surgery, demonstrating that tumours become potentially more friable and easier to disseminate in surgeons who are less experienced or where instrumentation is sub-optimal.
Similar content being viewed by others
References
Sain AH (1996) Laparoscopic cholecystectomy is the current “gold standard” for the treatment of gallstone disease. Ann Surg 224:689–690
Jakeways MS, Mitchell V, Hashim IA, Chadwick SJ, Shenkin A, Green CJ, Carli F (1994) Metabolic and inflammatory responses after open or laparoscopic cholecystectomy. Br J Surg 81:127–131
Kloosterman T, von Blomberg BM, Borgstein P, Cuesta MA, Scheper RJ, Meijer S (1994) Unimpaired immune functions after laparoscopic cholecystectomy. Surgery 15:424–428
Reissman P, Teoh TA, Skinner K, Burns JW, Wexner SD (1996) Adhesion formation after laparoscopic anterior resection in a porcine model: a pilot study. Surg Laparosc Endosc 6:136–139
Ng C, Whelan RL, Lacy AM, Yim AP (2005) Is minimal access surgery for cancer associated with immunologic benefits? World J Surg 29:975–981
Wexner SD, Cohen SM (1995) Port site metastases after laparoscopic colorectal surgery for cure of malignancy [see comments]. Br J Surg 82:295–298
Paolucci V, Schaeff B, Schneider M, Gutt C (1999) Tumor seeding following laparoscopy: international survey. World J Surg 23:989–995; discussion 996–997
Hughes ES, McDermott FT, Polglase AL, Johnson WR (1983) Tumor recurrence in the abdominal wall scar tissue after large-bowel cancer surgery. Dis Colon Rectum 26:571–572
Lacy AM, Garcia-Valdecasas, Delgado S, Castells A et al (2002) Laparoscopic assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial. Lancet 359:2224–2229
The clinical outcomes of surgical therapy study group (2004) A comparison of laparoscopically assisted and open colectomy for colon cancer. New Engl J Med 350:2050–2059
Guillou PJ, Quirke P, Thorpe H, Walker J, Jayne DG et al (2005) Short term endpoints of conventional versus laparoscopic assisted surgery in patients with colorectal cancer (MRC-CLASICC trial): multicentre randomised trial. Lancet 365:1718–1726
Reilly WT, Nelson H, Schroeder G, Wieand HS, Bolton J, O’Connell MJ (1996) Wound recurrence following conventional treatment of colorectal cancer. A rare but perhaps underestimated problem. Dis Colon Rectum 39:200–207
Klossner J, Kivisaari J, Niinikoski J (1974) Oxygen and carbon dioxide tensions in the abdominal cavity and colonic wall of the rabbit. Am J Surg 127:711–715
Ridgway P, Smith A, Ziprin P, Paraskeva P, Peck D, Darzi A (2002) Pneumoperitoneum augmented tumour invasiveness is abolished by matrix metalloprotease blockade. Surg Endosc 16:533–536
Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Bean JM, Prosni LR, Dewhirst MW (1996) Tumour oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 56(5):941–943
Pitson G, Fyles A, Milosevic M, Wylie J, Pintilie M, Hill R (2001) Tumour size and oxygenation are independent predictors of nodal diseases in patients with cervix cancer. Int J Radiat Oncol Biol Phys 51(3):699–703
Fyles A, Milosevic M, Hedley D, Pintilie M, Levin W, Manchul L, Hill RP (2002) Tumour hypoxia has independent predictor impact only in patients with node-negative cancer. J Clin Oncol 20(3):680–687
Cuvier C, Jang A, Hill RP (1997) Exposure to hypoxia, glucose starvation and acidosis: effect on invasive capacity of murine tumor cells and correlation with cathepsin (L + B) secretion. Clin Exp Metastasis 15:19–25
Grimm E, Bonavida B (1979) Mechanism of cell-mediated cytotoxicity at the single cell level. I. Estimation of cytotoxic T lymphocyte frequency and relative lytic efficiency. J Immunol 123:2861–2869
Young SD, Hill RP (1990) Effects of reoxygenation on cells from hypoxic regions of solid tumors: analysis of transplanted murine tumors for evidence of DNA overreplication. Cancer Res 50:5031–5038
Hasan NM, Adams GE, Joiner MC, Marshall JF (1998) Hypoxia facilitates tumour cell detachment by reducing expression of surface adhesion molecules and adhesion to extracellular matrix without loss of cell viability. Br J Can 77:1799–1805
Moll R, Mitze M, Frixen UH, Birchmeier W (1993) Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol 143:1731–1742
Thomas GJ, Jones J, Speight PM (1997) Integrins and oral cancer. Oral Oncol 33:381–388
Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW (1997) Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 38:285–289
Hockel M, Schlenger K, Aral B, Mitze M, Schaffer U, Vaupel P (1996) Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56:4509–4515
Hockel M, Vorndran B, Schlenger K, Baussmann E, Knapstein PG (1993) Tumor oxygenation: a new predictive parameter in locally advanced cancer of the uterine cervix. Gynecol Oncol 51:141–149
Basson MD, Yu CF, Herden-Kirchoff O, Ellermeier M, Sanders MA, Merrell RC, Sumpio BE (2000) Effects of increased ambient pressure on colon cancer cell adhesion. J Cell Biochem 78:47–61
Serrano CV Jr., Fraticelli A, Paniccia R, Teti A, Noble B, Corda S, Faraggiana T, Ziegelstein RC, Zweier JL, Capogrossi MC (1996) pH dependence of neutrophil-endothelial cell adhesion and adhesion molecule expression. Am J Physiol 271:C962–C970
Zirngibl H, Husemann B, Hermanek P (1990) Intraoperative spillage of tumor cells in surgery for rectal cancer. Dis Colon Rectum 33:610–614
van den Tol PM, van Rossen EE, van Eijck CH, Bonthuis F, Marquet RL, Jeekel H (1998) Reduction of peritoneal trauma by using nonsurgical gauze leads to less implantation metastasis of spilled tumor cells. Ann Surg 227:242–248
Author information
Authors and Affiliations
Corresponding author
Additional information
This project was jointly supervised by D.H. Peck and A.W. Darzi
Rights and permissions
About this article
Cite this article
Paraskeva, P.A., Ridgway, P.F., Olsen, S. et al. A surgically induced hypoxic environment causes changes in the metastatic behaviour of tumours in vitro. Clin Exp Metastasis 23, 149–157 (2006). https://doi.org/10.1007/s10585-006-9028-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10585-006-9028-8