title: Integrin αvβ3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells.
abstract: The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin αvβ3 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 αvβ3 ligands, activated growth-related signaling pathways in T-cell lymphomas (TCLs). Specifically, TH-activated αvβ3 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 αvβ3 decreased VEGF production and induced TCL cell death in vitro and in human xenograft models. In sum, we show that integrin αvβ3 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.
authors.affiliation: Neuroimmunomodulation and Molecular Oncology Department, Institute for Biomedical Research (BIOMED), National Research Council of Argentina (CONICET), Catholic University of Argentina (UCA), Buenos Aires, Argentina;
authors.forename: Florencia
authors.initials: F
authors.lastname: Cayrol
authors.affiliation: Neuroimmunomodulation and Molecular Oncology Department, Institute for Biomedical Research (BIOMED), National Research Council of Argentina (CONICET), Catholic University of Argentina (UCA), Buenos Aires, Argentina;
authors.forename: María Celeste
authors.initials: MC
authors.lastname: Díaz Flaqué
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY;
authors.forename: Tharu
authors.initials: T
authors.lastname: Fernando
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY;
authors.forename: Shao Ning
authors.initials: SN
authors.lastname: Yang
authors.affiliation: Neuroimmunomodulation and Molecular Oncology Department, Institute for Biomedical Research (BIOMED), National Research Council of Argentina (CONICET), Catholic University of Argentina (UCA), Buenos Aires, Argentina;
authors.forename: Helena Andrea
authors.initials: HA
authors.lastname: Sterle
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Foundation Institute Leloir-IIBBA, Buenos Aires, Argentina;
authors.forename: Marcela
authors.initials: M
authors.lastname: Bolontrade
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Foundation Institute Leloir-IIBBA, Buenos Aires, Argentina;
authors.forename: Mariana
authors.initials: M
authors.lastname: Amorós
authors.affiliation: Department of Nutritional Biochemistry, CONICET, National University of Tucumán, and Institute of Biological Chemistry "Dr Bernabé Bloj," San Miguel de Tucumán, Tucumán, Argentina;
authors.forename: Blanca
authors.initials: B
authors.lastname: Isse
authors.affiliation: Department of Nutritional Biochemistry, CONICET, National University of Tucumán, and Institute of Biological Chemistry "Dr Bernabé Bloj," San Miguel de Tucumán, Tucumán, Argentina;
authors.forename: Ricardo Norberto
authors.initials: RN
authors.lastname: Farías
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY;
authors.forename: Haelee
authors.initials: H
authors.lastname: Ahn
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY;
authors.forename: Ye F
authors.initials: YF
authors.lastname: Tian
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, NY; and.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tabbò
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY;
authors.forename: Ankur
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, NY; and.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Inghirami
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY;
authors.forename: Leandro
authors.initials: L
authors.lastname: Cerchietti
authors.affiliation: Neuroimmunomodulation and Molecular Oncology Department, Institute for Biomedical Research (BIOMED), National Research Council of Argentina (CONICET), Catholic University of Argentina (UCA), Buenos Aires, Argentina; Radioisotope Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Graciela Alicia
authors.initials: GA
authors.lastname: Cremaschi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D019169:Jurkat Cells; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012910:Snake Venoms / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013963:Thyroid Hormones / Q000235:genetics* / Q000276:immunology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology
chemical_list: D039302:Integrin alphaVbeta3; D034741:RNA, Small Interfering; D012910:Snake Venoms; D013963:Thyroid Hormones; D042461:Vascular Endothelial Growth Factor A; C422910:Cilengitide