Afg. Stevenson et Cs. Lange, EXTRACELLULAR-MATRIX (ECM) AND CYTOSKELETAL MODULATION OF CELLULAR RADIOSENSITIVITY, Acta oncologica, 36(6), 1997, pp. 599-606
Modulation of radiosensitivity by components of the extracellular matr
ix (ECM) and cytoskeletal elements has not been adequately studied. Al
though differences in the radiosensitivities of cells grown as monolay
ers, as spheroids, or grown in vitro in animal models are known, expla
nations have in the past neglected possible influences by the ECM and
cytoskeleton. Using collagen gel cultures, it is shown that the fibril
lar component of the ECM (which is responsible for cell anchorage) ind
uces shifts in radiosensitivity. The effect is critically dependent on
the affinity of the cell type towards collagen. The shifts in radiose
nsitivity induced by ECM alteration are manifested as changed D-q valu
es. By applying four specific cytoskeletal poisons which either stabil
ize or destabilize specific cytoskeletal elements, the involvement of
microfilaments and microtubuli was qualitatively appraised. Cytochalas
in B, which destabilizes microfilaments (by preventing polymerization)
, caused a significant rise in radioresistance. This rise was due to i
ncreased D-0. Although the cellular morphological change accompanying
cytochalasin B treatment was essentially similar to that obtained with
trypsin, the respective shifts in radioresponses were qualitatively d
ifferent and opposite, suggesting differences in mechanism of action.