Article: Cayrol, F; Flaque, MCD; Fernando, T; Yang, SN; Sterle, HA; Bolontrade, M; Amoros, M; Isse, B; Farias, RN; Ahn, H; Tian, YF; Tabbo, F; Singh, A; Inghirami, G; Cerchietti, L; Cremaschi, GA; (2015) “Integrin Alpha V Beta 3 Acting as Membrane Receptor for Thyroid Hormones Mediates Angiogenesis in Malignant T Cells”, Blood, 125(5):841-851
Abstract: The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin alpha v beta 3 allows tumor survival
and growth. This integrin was demonstrated to be the membrane receptor for thyroid hormones (THs) in several tissues. We found that THs, acting as soluble integrin alpha v beta 3 ligands, activated growth-related signaling pathways in T-cell lymphomas (TCLs). Specifically, TH-activated alpha v beta 3 integrin signaling promoted TCL proliferation and angiogenesis, in part, via the upregulation of vascular endothelial growth factor (VEGF). Consequently, genetic or pharmacologic inhibition of integrin alpha v beta 3 decreased VEGF production and induced TCL cell death in vitro and in human xenograft models. In sum, we show that integrin alpha v beta 3 transduces prosurvival signals into TCL nuclei, suggesting a novel mechanism for the endocrine modulation of TCL pathophysiology. Targeting this mechanism could constitute an effective and potentially low-toxicity chemotherapy-free treatment of TCL patients.
National Institutes of Health, National Cancer Institute [R21 CA185236]; National Research Council of Argentina [PIP-CONICET 00275]; University of Buenos Aires [UBACYT 20020130100289BA]; National Agency for Science and Technology (ANPCYT) [PICT 20081858]; National Agency for Science and Technology [PICT-Raices 2012-1328]; Malvin Peace Sevin Research Scholar Award; Irma T. Hirschl Career Scientist Award; Cutaneous Lymphoma Foundation CLARIONS Research Award; Italian Association for Cancer Research Special Program in Clinical Molecular Oncology ; Jorge Oster Award from the Bunge and Born Foundation
L.C. is the Raymond and Beverly Sackler Scholar and Scholar of the American Society of Hematology. This work was supported by the National Institutes of Health, National Cancer Institute (R21 CA185236) (L.C. and A.S.), the National Research Council of Argentina (PIP-CONICET 00275) (G.A.C.), the University of Buenos Aires (UBACYT 20020130100289BA) (G.A.C.), the National Agency for Science and Technology (ANPCYT, PICT 20081858) (G.A.C.) (PICT-Raices 2012-1328) (G.A.C. and L.C.), the Malvin Peace Sevin Research Scholar Award (L.C.), the Irma T. Hirschl Career Scientist Award (L.C.), the Cutaneous Lymphoma Foundation CLARIONS Research Award (L.C.), the Italian Association for Cancer Research Special Program in Clinical Molecular Oncology (5×1000 no. 10007) (G.I.), and the Jorge Oster Award from the Bunge and Born Foundation (F.C.).