Journal
ONCOTARGETS AND THERAPY
Volume 7, Issue -, Pages 1619-1624Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S67393
Keywords
integrin; thyroid hormone; thyroxine; antiangiogenesis; proapoptosis
Categories
Ask authors/readers for more resources
The extracellular domain of integrin alpha v beta 3 contains a receptor for thyroid hormone and hormone analogs. The integrin is amply expressed by tumor cells and dividing blood vessel cells. The proangiogenic properties of thyroid hormone and the capacity of the hormone to promote cancer cell proliferation are functions regulated nongenomically by the hormone receptor on alpha v beta 3. An L-thyroxine (T-4) analog, tetraiodothyroacetic acid (tetrac), blocks binding of T-4 and 3,5,3'-triiodo-L-thyronine (T-3) by alpha v beta 3 and inhibits angiogenic activity of thyroid hormone. Covalently bound to a 200 nm nanoparticle that limits its activity to the cell exterior, tetrac reformulated as Nanotetrac has additional effects mediated by alpha v beta 3 beyond the inhibition of binding of T-4 and T-3 to the integrin. These actions of Nanotetrac include disruption of transcription of cell survival pathway genes, promotion of apoptosis by multiple mechanisms, and interruption of repair of double-strand deoxyribonucleic acid breaks caused by irradiation of cells. Among the genes whose expression is suppressed by Nanotetrac are EGFR, VEGFA, multiple cyclins, catenins, and multiple cytokines. Nanotetrac has been effective as a chemotherapeutic agent in preclinical studies of human cancer xenografts. The low concentrations of alpha v beta 3 on the surface of quiescent nonmalignant cells have minimized toxicity of the agent in animal studies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available