Mechanisms involved in the early interaction between HeLa cells, platelets and endothelial cells in vitro under the influence of thrombin. Effects of acetylsalicylic acid and Na-salicylate.

The aim of the study was to obtain more information about the mechanisms involved in the initial adhesion of tumour cells to endothelial cell during metastasis. In a previous paper, we found that addition of both platelets and thrombin increased the adhesion of tumour cells to cultured endothelial cells within 15 min, compared to when either one or both of the ingredients were absent. In the present study, HeLa cells, prelabelled with radioactive 51Cr, human platelets, and thrombin, were added to the medium in dishes of endothelial cells. The dishes were then shaken for 15 min at 37 degrees C. Scanning and transmission electron micrographs showed HeLa cells adhering to the endothelium either together with platelets or without them. In other experiments, the endothelium was pretreated for 30 min with either of the following: 0.5 mM or 0.1 mM acetylsalicylic acid (ASA); 0.5 mM or 0.1 mM Na-salicylate (NaS). Pretreatment of the endothelium with 0.5 mM ASA significantly increased the percentage of adherent tumour cells, while 0.1 mM ASA and the two concentrations of NaS caused only minor changes. In addition, the ASA-treatment caused more HeLa cells to adhere without platelets while NaS-treatment caused more HeLa cells to adhere together with platelets. Release of 51Cr from HeLa cells during the experimental period was also measured; the addition of thrombin and platelets did not change the 51Cr release significantly. In separate experiments, HeLa cells and platelets were mixed without the presence of endothelial cells. Transmission electron micrographs showed that in the absence of thrombin, mixed HeLa cells and platelets did not react with each other; when thrombin was added they formed co-aggregates. In conclusion, we show that in our experimental model HeLa cells adhere to the endothelium in two ways, both with and without platelets. The production of prostacyclin in the endothelial cells has an inhibitory effect on tumour cell adhesion. Without thrombin, the HeLa cells are not capable of activating platelets.