Expression of angiogenic switch, cachexia and inflammation factors at the crossroad in undifferentiated thyroid carcinoma with BRAFv600E

被引：9

作者：

Husain, Amjad ^{[1
]}

Hu, Nina ^{[2
]}

Sadow, Peter M. ^{[3
]}

Nucera, Carmelo ^{[1
]}

机构：

[1] Harvard Med Sch, Vasc Biol Res Ctr, BIDMC, Boston, MA 02115 USA

[2] Harvard Med Sch, Lab Human Thyroid Canc Preclin & Translat Res, Div Canc Biol & Angiogenesis, CRI,Canc Ctr,Dept Pathol,Beth Israel Deaconess Me, Boston, MA USA

[3] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA

来源：

CANCER LETTERS | 2016年 / 380卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Anaplastic thyroid cancer; Cachexia; Cytokines; Angiogenesis; Inflammation; BRAF(V600E); ENDOTHELIAL GROWTH-FACTOR; ORTHOTOPIC MOUSE MODEL; BRAF V600E MUTATION; CANCER CACHEXIA; DISTANT METASTASIS; NUDE-MICE; CELL-LINE; PHASE-II; TUMOR; CYTOKINES;

D O I：

10.1016/j.canlet.2015.07.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cachexia is the result of complex metabolic alterations which cause morbidity and mortality in patients with advanced cancers including undifferentiated (anaplastic) thyroid carcinoma (ATC). ATC is a lethal disease with limited therapeutic options and unclear etiology for cachexia. We hypothesize that the BRAF(V600E) oncoprotein triggers microvascular endothelial cell tubule formation (in vitro angiogenesis) by means of factors which play a crucial role in angiogenic switch, inflammation/immune response and cachexia. We use human ATC cells and applied multiplex ELISA assay to screen for and measure angiogenic/cachectic and pro-inflammatory factors in the ATC-derived secretome. We find that vemurafenib anti-BRAF(V600E) therapy significantly reduces secreted VEGFA, VEGFC and IL6 protein levels compared to vehicle treated ATC cells. As a result, the secretome from vemurafenib-treated ATC cells inhibits microvascular endothelial cell-related in vitro angiogenesis. Furthermore, ATC clinical samples express VEGFA, VEGFC and IL6 proteins. Our results suggest that angiogenic/cachectic and pro-inflammatory/immune response factors could play a crucial role in BRAF(V600E)-positive human ATC aggressiveness. Understanding the extent to which,microenvironment-associated angiogenic factors participate in cachexia and cancer metabolism in advanced thyroid cancers will reveal new biomarkers and foster novel therapeutic approaches. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：577 / 585

页数：9

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