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Lethal deformation of cancer cells in the microcirculation: A potential rate regulator of hematogenous metastasis
Author(s) -
Weiss L.,
Nannmark U.,
Johansson B. R.,
Bagge U.
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910500121
Subject(s) - regulator , microcirculation , metastasis , cancer metastasis , cancer , medicine , pathology , cancer research , biology , biochemistry , gene
The hypothesis has been advanced that deformation‐induced lethal mechanical trauma, resulting in surface‐membrane rupture, is inflicted on circulating cancer cells trapped in the microcirculation, and that this rapid cell‐killing mechanism is a potentially important rate regulator for hematogenous metastasis. We describe and discuss an in vivo test of this hypothesis. Vital fluorescence microscopy was performed on the microcirculation of cremaster muscle preparations in mice, following retrograde injections into the femoral artery of acridine orange‐stained sarcoma cells. Cancer cells having mean diameters of 16.5 μm in suspension, were deformed from spheres into cylinders having a mean length of 53 μm, in 7‐μm diameter capillaries. Most of these cells were dead several minutes after injection. It was estimated that sphere‐to‐cylinder shape‐transitions of this magnitude required an average increase of 52% in apparent cell surface area. Evidence is presented that most of this apparent increase was achieved by non‐lethal surface “unfolding”, utilizing membrane “excess”. That cancer‐cell deformation of the magnitude observed in vivo is the direct cause of lethal, surface‐membrane rupture was indicated by the observed loss of membrane integrity in cells deformed from spherical to cylindrical shape in vitro, by aspiration into micropipettes of capillary dimensions. The experimental observations are therefore consistent with the hypothesis.