The role of thrombospondin-1 in tumor progression and angiogenesis.
Thrombospondin (TSP-1) is a large glycoprotein secreted by platelets and synthesized by many cell types, including endothelial and tumor cells. Although controversy exists about the biological function of TSP-1, the following observations suggest that TSP-1 may potentiate tumor progression. (1) Tumor metastases in mice are promoted by TSP-1 and inhibited by anti-TSP-1 antibodies. (2) TSP-1 promotes tumor cell adhesion, migration and invasion. (3) TSP-1 promotes angiogenesis in the rat aorta model. (4) TSP-1 up-regulates the plasminogen activator system through a mechanism involving the activation of TGF-beta 1. (5) Human tumors express increased levels of the CSVTCG-specific TSP-1 receptor. (6) Tumor stroma is enriched in TSP-1. (7) Cancer patients have high blood levels of TSP-1. (8) Poor patient survival correlates with a higher expression of the CSVTCG-specific TSP-1 receptor on tumor cells. In this paper we discuss the evidence that TSP-1 promotes tumor progression and present a hypothetical scheme for its mechanism of action.
Tuszynski
G P
GP
Department of Surgery, Medical College of Pennsylvania, Philadelphia, USA.
Nicosia
R F
RF
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D018955:CD36 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D019699:Thrombospondins
D018955:CD36 Antigens; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D019699:Thrombospondins