Thalidomide may impede cell migration in primates by down-regulating integrin beta-chains: potential therapeutic utility in solid malignancies, proliferative retinopathy, inflammatory disorders, neointimal hyperplasia, and osteoporosis.
A growing number of human inflammatory disorders are reported to respond to treatment with thalidomide, and recently this drug has been shown to inhibit angiogenesis in the rabbit, in doses which can elicit teratogenicity in this species. Studies in marmosets and humans indicate that thalidomide, and a teratogenic analogue, decrease the expression of beta integrin subunits, most notably beta 3 and the beta 2 produced by leukocytes. Since integrins are crucial for cell-matrix interactions, and the beta 2 integrins of leukocytes mediate adhesion to endothelium, it is reasonable to postulate that thalidomide inhibits cell migration in susceptible species, and that this accounts for its anti-inflammatory, anti-angiogenic, and teratogenic activity. This perspective suggests that thalidomide will show utility in the prevention or treatment of a wide range of disorders, including solid tumors, proliferative retinopathies, many inflammatory diseases, neointimal hyperplasia, and osteoporosis. It is likely that dietary fish oil-as well as selective inhibitors of urokinase, when and if they become clinically available-will complement the efficacy of thalidomide in most if not all of these applications.
McCarty
M F
MF
Nutrition 21, San Diego, CA 92109, USA.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002144:Callithrix; D005395:Fish Oils; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000188:drug therapy; D016023:Integrins / Q000096:biosynthesis*; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D011323:Primates; D011817:Rabbits; D012164:Retinal Diseases / Q000188:drug therapy*; D013723:Teratogens; D013792:Thalidomide / Q000494:pharmacology* / Q000627:therapeutic use*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D014652:Vascular Diseases / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D005395:Fish Oils; D016023:Integrins; D013723:Teratogens; D013792:Thalidomide