Examination of a system for the mechanistic study of tumor cell-platelet interactions under well-defined flow conditions
Jain, Hayuta Z.
McIntire, Larry V.
Master of Science
The compelling evidence that platelets play a contributory role in hematogenous metastasis raises a need to elucidate the molecular mechanisms by which tumor cells activate and adhere to platelets. To model the in vivo interactions of platelets with arrested tumor cells, heparinized mepacrine-labeled whole blood was perfused over an A875 melanoma cell monolayer in a parallel plate flow chamber at shear rates characteristic of the microvasculature. Epi-fluorescence video microscopy utilizing a cooled CCD camera and digital image processing were used to quantify the dynamic adhesion and aggregation of platelets. Varying the exposure time of the monolayer to the 445 nm excitation wavelength revealed that photoactivation was stimulating the tumor cells and that the cells were relatively nonthrombogenic in absence of the light over the time scale of the flow experiments. Preactivation of the tumor cells was attempted with 12(S)-HETE, thrombin, and TNF-alpha and resulted in close to no platelet deposition.
Cell biology; Biophysics; Oncology; Biology; Health sciences