Integrin alphaVbeta3 transduces survival and angiogenic signals to T cell lymphomas and is a therapeutic target.

CAYROL, MARIA FLORENCIA; DIAZ FLAQUE, MARIA CELESTE; THARU, FERNANDO; SHAO NING YANG; BOLONTRADE, MARCELA F.; AMORÓS, MARIANA A.; FARÍAS, RICARDO; INGHIRAMI, GIORGIO; CREMASCHI, GRACIELA; CERCHIETTI, LEANDRO

San Francisco

Simposio; 56th Annual Meeting and Exposition, American Society of Hematology; 2014

American Society of Hematology

Malignant Tcell proliferation, survival and drug resistant are dependent on a combination of externa! Stimuli delivered by the microenvironment. Previous studies have shown that the transmembrane receptor integrin V3plays a critical role mediating the interaction of T cell lymphoma (TCL) cells with externa! signals. lntegrin V3 ligands include extracellular matrix-assoc:iated signaling proteni s and soluble factors such as thyroid hormones (TH).We have also shown that THs stlmulate the proliferatlon of TCLs throughl complementary lntracellular pathways involvlng the V3 integrin. We therefore hypotheslzed that targetlng lntegrin V3 could represent a novel strategy to treat TCL patlents. To determine survlval pathways lnduced by TH on V3 integrlns, we evatuated the transcriptional changes (RNA-seq) lnduced by physlologlcal concentratlons of cell impermeable T3/T4 coupled to agarose (TH-AG) vs. control ln the TCL cell line CUTLL1.We ldentlfled 123 up- and down-regulated transcrlpts (p