Anti‐JAM‐C therapy eliminates tumor engraftment in a xenograft model of mantle cell lymphoma

[摘要] Junctionaladhesionmolecule(JAM)‐CisamemberoftheJAMfamily,expressedbyavarietyofdifferentcelltypes,includinghumanBlymphocytesandsomeB‐celllymphomasubtypes—inparticular,mantlecelllymphoma(MCL).Treatmentwithanti‐JAM‐CpAbsreduceshomingofhumanBcellstolymphoidorgansinaNOD/SCIDmousemodel.Inthepresentstudy,theroleofJAM‐CintheengraftmentofhumanlymphomaBcellsinmicewasinvestigated.Administrationofnovelanti‐JAM‐CmAbsreducedtumorgrowthofJAM‐C+MCLcellsinbonemarrow,spleen,liver,andlymphnodesofmice.Treatmentwithanti‐JAM‐CantibodiessignificantlyreducedtheproliferationofJAM‐C‐expressinglymphomaBcells.Moreover,thebindingofanti‐JAM‐CantibodiesinhibitedthephosphorylationofERK1/2,withoutaffectingothersignalingpathways.TheresultsidentifyforthefirsttimetheintracellularMAPKcascadeastheJAM‐C‐drivensignalingpathwayinJAM‐C+Bcells.TargetingJAM‐CcouldconstituteanewtherapeuticstrategyreducinglymphomaB‐cellproliferationandtheircapacitytoreachsupportivelymphoidmicroenvironments...

[学科分类] 生理学

[关键词] B‐cell homing;B‐cell proliferation;mantle cell lymphoma treatment