Platelet involvement during
tumor cell adhesion to subendothelial matrix was examined in vitro. Platelets were subjected to
thrombin stimulation and mechanical lysis and examined for their effects on
tumor cell adhesion. These treatments altered the platelet ultrastructure and cytoskeletal integrity. Untreated washed rat platelets (WRP) exhibited extensive adhesion to and spreading on substrates and substantially enhanced
tumor cell adhesion to the same substrates (i.
e., 250% greater than
tumor cells without platelets).
Thrombin prestimulation of platelets limited platelet adhesion and spreading and platelet facilitation of
tumor cell adhesion. Complete mechanical lysis disrupted both the platelet membrane and the cytoskeleton and eliminated the ability of platelets to adhere or to enhance
tumor cell adhesion. Partially lysed platelets resembled membrane ghosts and facilitated
tumor cell adhesion by a mechanism independent of spreading and cytoskeletal rearrangement. Fractionation studies indicated that platelet cytoskeletal components played a role in the adhesion process. Pretreatment of WRP with
cytochalasin A or B dose dependently inhibited microfilament-mediated platelet spreading and platelet-enhanced
tumor cell adhesion.
Colchicine and
vinblastine induced microtubule depolymerization, but they had no observable effect on platelet spreading or platelet-enhanced
tumor cell adhesion. It was concluded that platelet-enhanced
tumor cell adhesion to subendothelial matrix depends on an intact platelet cytoskeleton and on a platelet membrane component(s) and is mediated by surface contact between platelets and
tumor cells. Furthermore, platelet-mediated
tumor cell adhesion to subendothelial matrix may involve two mechanisms: one dependent on, and one independent of, platelet spreading and cytoskeletal rearrangement.