title: A surgically induced hypoxic environment causes changes in the metastatic behaviour of tumours in vitro.
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 1alpha (HIF-1alpha). 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 beta1 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.
authors.affiliation: Department of Biosurgery & Surgical Technology, Division of Surgery, Oncology, Reproductive Biology and Intensive Care, Imperial College London, St Mary's Hospital, London, UK. p.paraskevas@imperial.ac.uk
authors.forename: P A
authors.initials: PA
authors.lastname: Paraskeva
authors.forename: P F
authors.initials: PF
authors.lastname: Ridgway
authors.forename: S
authors.initials: S
authors.lastname: Olsen
authors.forename: C
authors.initials: C
authors.lastname: Isacke
authors.forename: D H
authors.initials: DH
authors.lastname: Peck
authors.forename: A W
authors.initials: AW
authors.lastname: Darzi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D015820:Cadherins / Q000378:metabolism; D002245:Carbon Dioxide / Q000009:adverse effects; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015687:Cell Hypoxia; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006371:Helium / Q000009:adverse effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D010535:Laparoscopy / Q000009:adverse effects*; D009362:Neoplasm Metastasis; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D002245:Carbon Dioxide; D006371:Helium