Platelet-tumor cell interaction with the subendothelial extracellular matrix: relationship to cancer metastasis.
Dissemination of neoplastic cells within the body involves invasion of blood vessels by tumor cells. This requires adhesion of blood-borne cells to the luminal surface of the vascular endothelium, invasion through the endothelial cell layer and local dissolution of the subendothelial basement membrane. Platelets may participate in each of these steps and thus play a role in the pathogenesis of tumor cell metastasis. To learn more about the possible involvement of platelets we studied the interaction of platelets and tumor cells with cultured vascular endothelial cells and their secreted basement membrane-like extracellular matrix (ECM). Whereas the apical surface of the vascular endothelium lacks adhesive glycoproteins and hence protect the vessel wall against platelet and tumor cell adhesion, the underlying ECM constitute a highly adhesive and thrombogenic surface. Interaction of platelets with this ECM was associated with platelet activation, aggregation and degradation of heparan sulfate in the ECM by means of the platelet heparitinase. The activity of a similar enzyme has been previously correlated with the metastatic potential of various tumor sublines. Biochemical and scanning electron microscopy (SEM) studies have demonstrated that platelets may detect even minor gaps between adjacent endothelial cells and degrade the ECM heparan sulfate. This may expose a larger area of the subendothelium and facilitate subsequent adhesion of blood borne tumor cells. Platelets were also shown to recruit lymphoma cells into minor gaps in the vascular endothelium, that otherwise do not constitute a preferential site of invasion. It is suggested that the platelet heparitinase is involved in the impairment of the integrity of the vessel wall and thus play a role in tumor cell metastasis.
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology / Q000502:physiology*; D001808:Blood Vessels / Q000648:ultrastructure; D002417:Cattle; D002450:Cell Communication; D004727:Endothelium / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009369:Neoplasms / Q000503:physiopathology*; D011133:Polysaccharide-Lyases / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism
D011509:Proteoglycans; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase