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Extracellular Matrix (ECM) and Cytoskeletal Modulation of Cellular Radiosensitivity
Journal Title
Acta Oncologica
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Term and Year
Publication Date
2009-07-08
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Publication Volume
36
Publication Issue
6
Publication Begin
599
Publication End
606
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Abstract
Modulation of radiosensitivity by components of the extracellular matrix (ECM) and cytoskeletal elements has not been adequately studied. Although differences in the radiosensitivities of cells grown as monolayers, as spheroids, or grown in vitro in animal models are known, explanations have in the past neglected possible influences by the ECM and cytoskeleton. Using collagen gel cultures, it is shown that the fibrillar component of the ECM (which is responsible for cell anchorage) induces shifts in radiosensitivity. The effect is critically dependent on the affinity of the cell type towards collagen. The shifts in radiosensitivity induced by ECM alteration are manifested as changed Dq values. By applying four specific cytoskeletal poisons which either stabilize or destabilize specific cytoskeletal elements, the involvement of microfilaments and microtubuli was qualitatively appraised. Cytochalasin B, which destabilizes microfilaments (by preventing polymerization), caused a significant rise in radioresistance. This rise was due to increased D0. Although the cellular morphological change accompanying cytochalasin B treatment was essentially similar to that obtained with trypsin, the respective shifts in radioresponses were qualitatively different and opposite, suggesting differences in mechanism of action.
Citation
Stevenson AF, Lange CS. Extracellular matrix (ECM) and cytoskeletal modulation of cellular radiosensitivity. Acta Oncol. 1997;36(6):599-606. doi: 10.3109/02841869709001322. PMID: 9408150.