Endostatinisanaturally-occurring20-kDaC-terminalfragmentderivedfromtypeXVIIIcollagen.Itisreportedtoserveasananti-angiogenicagent,similartoangiostatinandthrombospondin.AnditisproducedbyproteolyticcleavageofcollagenXVIII,amemberofthemultiplexinfamilythatischaracterizedbyinterruptionsinthetriplehelixcreatingmultipledomains,byproteasessuchascathepsins.Usingagenomiccloneasaprobeforfluorescenceinsituhybridization,EndostatinwasmappedtheCOL18A1geneto21q22.3.Byimmunoprecipitationanalysisusingmembranefractionsofhumanmammaryepithelialcells,Itshowedthatendostatinspecificallyboundtocellsurfacenucleolinwithhighaffinity.BlockageofnucleolinwithneutralizingantibodyorknockdownofnucleolinbyRNAinterferencecounteredtheantiendothelialactivityofendostatinandabrogateditsantiangiogenicandantitumoractivityinvivo.