Fibroblast growth factor receptor is a mechanistic link between visceral adiposity and cancer.
Fibroblast growth factor receptor is a mechanistic link between visceral adiposity and cancer.
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DOI：
10.1038/onc.2017.278
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发表时间：
2017-11-30
期刊：
影响因子：
8
通讯作者：
Bernard JJ
中科院分区：
文献类型：
--
作者：
Chakraborty D;Benham V;Bullard B;Kearney T;Hsia HC;Gibbon D;Demireva EY;Lunt SY;Bernard JJ
流行病学证据表明，脂肪组织过多会增加癌症风险。尽管全球肥胖患病率急剧上升，但肥胖如何促成转化（非致瘤细胞经历的恶性阶段）尚不清楚。为了确定脂肪组织中刺激转化的因素，我们使用了一种新的内脏脂肪组织（VAT）条件培养基刺激软琼脂中上皮细胞生长的离体系统。为了在体内扩展该系统，我们使用了紫外线B诱导的、VAT促进的皮肤肿瘤形成的小鼠脂肪切除模型。我们发现，从小鼠和肥胖的人捐助者的增值税刺激非致瘤性上皮细胞在软琼脂的生长。VAT活性的差异与成纤维细胞生长因子-2（FGF 2）水平相关。此外，人和小鼠VAT不能刺激缺乏FGFR-1（FGF 2受体）的细胞在软琼脂中的生长。我们还证明了FGF 2的循环水平与体内非黑色素瘤肿瘤形成相关。这些数据暗示FGF 2是VAT释放转化上皮细胞的一个主要因素，这是一种新的、潜在的VAT增强肿瘤发生的途径。旨在消耗腹部肥胖个体中FGF 2的VAT储存或抑制FGFR-1的策略可能是重要的癌症预防策略以及改善结果的辅助疗法。
Epidemiological evidence implicates excess adipose tissue in increasing cancer risk. Despite a steeply rising global prevalence of obesity, how adiposity contributes to transformation (stage a non-tumorigenic cell undergoes to become malignant) is unknown. To determine the factors in adipose tissue that stimulate transformation, we used a novel ex vivo system of visceral adipose tissue (VAT)-condition medium-stimulated epithelial cell growth in soft agar. To extend this system in vivo, we used a murine lipectomy model of ultraviolet light B-induced, VAT-promoted skin tumor formation. We found that VAT from mice and obese human donors stimulated growth in soft agar of non-tumorigenic epithelial cells. The difference in VAT activity was associated with fibroblast growth factor-2 (FGF2) levels. Moreover, human and mouse VAT failed to stimulate growth in soft of agar in cells deficient in FGFR-1 (FGF2 receptor). We also demonstrated that circulating levels of FGF2 were associated with non-melanoma tumor formation in vivo. These data implicate FGF2 as a major factor VAT releases to transform epithelial cells—a novel, potential pathway of VAT-enhanced tumorigenesis. Strategies designed to deplete VAT stores of FGF2 or inhibit FGFR-1 in abdominally obese individuals may be important cancer prevention strategies as well as adjuvant therapies for improving outcomes.
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影响因子：
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