Journal
BLOOD
Volume 125, Issue 5, Pages 841-851Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2014-07-587337
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Funding
- 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 [10007]
- Jorge Oster Award from the Bunge and Born Foundation
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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.
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