Astissuesgrowtheyrequireangiogenesistooccuriftheyaretobesuppliedwithbloodvesselsandsurvive.Factorsthatinhibitangiogenesismightactascancertherapeuticsbyblockingvesselformationintumorsandstarvingcancercells.Thrombospondin-1(TSP-1)isaproteinthatinhibitsangiogenesisandslowstumorgrowth,apparentlybyinducingapoptosisofmicrovascularendothelialcellsthatlinebloodvessels.TSP-1appearstoproducethisresponsebyactivatingasignalingpathwaythatbeginswithitsreceptorCD36atthecellsurfaceofthemicrovascularendothelialcell.Thenon-receptortyrosinekinasefynisactivatedbyTSP-1throughCD36,activatingtheapoptosisinducingproteaseslikecaspase-3andp38proteinkinases.p38isamitogen-activatedkinasethatalsoinducesapoptosisinsomeconditions,perhapsthroughAP-1activationandtheactivationofgenesthatleadtoapoptosis. Contributor:GlennCroston,PhD REFERENCES:BenildeJimenez,OlgaV.Volpert,SusanE.Crawford,MariaFebbraio,RoyL.Silberstein&NoelBouckSignalsleADIngtoapoptosis-dependentinhibitionofneovascularizationbythrombospondin-1.NatureMedicineJan2000,Vol6#1pp41-48
