title: Effect of extracorporal high hydrostatic pressure on tumor cell adherence and viability.
abstract: In orthopedic surgery, reconstruction of bone segments afflicted with cancer is done in various ways, including devitalization of the bone or replacement of the bone by artificial bone constructs. To devitalize bone cells, extracorporal irradiation or autoclaving is used although both methods have substantial disadvantages. We now introduce the technique of extracorporal high hydrostatic pressure (HHP) treatment to disintegrate tumor cells in suspension or in their adherent state. The effect of HHP on cell viability, adherence and morphology of four different tumor cell lines (fibrosarcoma HT-1080, osteosarcoma SAOS-2, ovarian cancer OV-MZ-6, breast cancer MCF-7) was investigated. For this, adherently growing (with fibronectin serving as the growth-promoting substrate) or suspended tumor cells were placed into a test vial which was transferred into the pressure chamber of a high hydrostatic pressure device. After pressure treatment, the pressure was relaxed to atmospheric pressure and subsequently cell viability, adherence and morphology assessed. High hydrostatic pressure as high as 350 MPa (10 min, 37 degrees C) did not detach the tumor cells from the fibronectin-coated surface although at these conditions all of the four cell lines tested were irreversibly damaged. Adherently growing tumor cells were considerably more sensitive to HHP than tumor cells detached from the surface and treated by HHP in suspension. HHP-treated tumor cells showed drastic morphological changes, evident by cell membrane ruffling and bleb formation. At 150 MPa adherently growing or suspended tumor cells are irreversibly damaged by short-term treatment with HHP. In another investigation, we experienced that treatment of freshly excised bones or tendons by HHP has no adverse effect on their stability or biomechanical properties. Therefore, we anticipate that in orthopedic surgery HHP could be used as a new gentle way of treating resected cancer-afflicted bones or tendons to inactivate tumor cells before autologous reimplantation.
authors.affiliation: Department of Orthopedic Surgery, Technical University of Munich, Germany. p.diehl@lrz.tum.de
authors.forename: Peter
authors.initials: P
authors.lastname: Diehl
authors.forename: Ute
authors.initials: U
authors.lastname: Reuning
authors.forename: Hans
authors.initials: H
authors.lastname: Gollwitzer
authors.forename: Ulla
authors.initials: U
authors.lastname: Magdolen
authors.forename: Ludger
authors.initials: L
authors.lastname: Gerdesmeyer
authors.forename: Johannes
authors.initials: J
authors.lastname: Schauwecker
authors.forename: Jutta
authors.initials: J
authors.lastname: Tuebel
authors.forename: Reiner
authors.initials: R
authors.lastname: Gradinger
authors.forename: Wolfram
authors.initials: W
authors.lastname: Mittelmeier
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D001842:Bone and Bones / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D006874:Hydrostatic Pressure; D009369:Neoplasms / Q000628:therapy*; D011312:Pressure; D013997:Time Factors
chemical_list: D005353:Fibronectins