Integrin αvβ3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells
Integrin αvβ3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells
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DOI：
10.1182/blood-2014-07-587337
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发表时间：
2015-01-29
期刊：
影响因子：
20.3
通讯作者：
Alicia Cremaschi, Graciela
中科院分区：
文献类型：
--
作者：
Cayrol, Florencia;Diaz Flaque, Maria Celeste;Alicia Cremaschi, Graciela
淋巴样肿瘤细胞通过整合素α v β 3与细胞外基质成分相互作用，使肿瘤存活和生长。该整合素在多个组织中被证明是甲状腺激素（THs）的膜受体。我们发现，THs作为可溶性整合素α v β 3配体，激活t细胞淋巴瘤（TCLs）的生长相关信号通路。具体来说，th激活的α v β 3整合素信号通过上调血管内皮生长因子（VEGF）促进TCL增殖和血管生成。因此，在体外和人类异种移植模型中，遗传或药物抑制整合素α v β 3可减少VEGF的产生并诱导TCL细胞死亡。总之，我们发现整合素α v β 3将促生存信号转导到TCL细胞核中，提示了TCL病理生理内分泌调节的新机制。针对这一机制可能构成一种有效且具有潜在低毒的TCL患者无化疗治疗方法。
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.