Effect of Hyperthermia on the Cytoskeleton and Focal Adhesion Proteins in a Human Thyroid Carcinoma Cell Line

Abstract

Hyperthermia is reported to act as a sensitizer to chemotherapeutic drugs in the treatment of cancer. Thyroid follicular carcinoma were used to elucidate the effects of hyperthermic treatment (41-430C) on cell morphology, cytoskeleton and the focal adhesion complex. The critical temperature that resulted in inhibition of cell proliferation as the cell number in the same area did not increase over a 23 hr- time course and irreversible changes in cell morphology was 42-43 0C. An immunofluorescence study on heat-treated cells (430C, 1-5 h) demonstrated that depolymerization of actin filaments, intermediate filaments and microtubules accounted for the rounding-up of cells and detachment from the substratum. Characteristic staining patterns for integrin av, focal adhesion kinase and vinculin were noted in untreated cells, but the immunoreactive intensities for these proteins became weaker with time of heat treatment. Anti-phosphotyrosine staining revealed less immunoreactivity in the focal adhesions in treated cells compared with control cells. The disappearance of integrin av from the cell surface may result in inhibition of integrin-mediated activation of focal adhesion kinase, which results in dephosphorylation of focal adhesion components and its disassembly. These results indicate that hyperthermia induces disruption of integrin-mediated actin cytoskeleton assembly and, possibly, of other integrin- mediated signaling pathways.