Cancer Res：肥胖患者有较高的癌症发病率和较差的预后

为什么肥胖的癌症患者要比那些苗条的癌症患者经常拥有更加差的预后不良？根据一项发表在Cancer Research期刊上的研究，研究人员可能发现了一种新的解释。

    美国德州大学休斯敦卫生科学中心分子医学研究所副教授Mikhail Kolonin博士说，“群体研究已鲜明地证实起肥胖和癌症癌症发病率之间存在关联。再者，就几种癌症而言，肥胖与更差的预后不良相关联。”

    Kolonin和他的同事们评估了肥胖如何促进癌症发展。他说，“我们早期的研究让我们假设在肥胖人体内增加的白色脂肪组织直接参与癌症发展，但是也比较重要的食物和生活方式并不直接参与。”

    他们的初步结果证实了这一假设：在吃相同食物的肥胖小鼠和苗条小鼠中，肿瘤在肥胖小鼠中的生长速度更快。研究人员还观察到相比于苗条的小鼠，在肥胖小鼠中有多得多的白色脂肪组织细胞(被称作脂肪基质细胞)，因此他们重点研究了这些细胞所发挥的作用。

    详细分析表明癌症诱导脂肪基质细胞进入血液循环。一旦位于肿瘤之中，一些脂肪基质细胞发育成脂肪细胞，而其他的脂肪基质细胞则被整合进肿瘤相关血管(tumor-associated blood vessel)中。

    肿瘤相关联血管通过带来在癌细胞的存活和增殖中发挥至关重要的氧气和营养物质而促进肿瘤生长。Kolonin注意到，脂肪基质细胞导致肿瘤相关血管形成的能力可能是肿瘤中这些过量细胞与增加的恶性肿瘤细胞增殖和肿瘤生长相关联的主要原因之一。

    Kolonin说，“我们的数据首次提供体内证据证实招募来自内源性脂肪组织的细胞到肿瘤之中。事实上，这些存在于肿瘤之中仍然是一个新兴的概念。我们不仅证实它们确实存在肿瘤之中，而且它们是有功能性的，并且影响肿瘤生长。鉴定出导致这些细胞被招募至肿瘤之中的信号和找到阻断这些信号的方法可能为人们提供一种新的癌症治疗方法。”

与肥胖相关的拓展阅读：

• Cancer Res：肥胖患者有较高的癌症发病率和较差的预后
• Eur Heart J：“肥胖悖论”：肥胖患者卒中后预后更佳？
• 组图：看看世界上最肥胖的人怎么生活？
• Arch Dermatol：牛皮癣患儿易肥胖
• Am J Cardiol：肥胖为高敏C反应蛋白升高最重要预测因素
• AIM：青少年肥胖与中年肾衰竭风险较高有关
• Diabetes Care：提高胰岛素敏感性减少肥胖者食物渴求
• 阿达木单抗或为肥胖银屑病患者最佳抗TNF药物
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doi: 10.1158/0008-5472.CAN-12-0294
Stromal Progenitor Cells from Endogenous Adipose Tissue Contribute to Pericytes and Adipocytes That Populate the Tumor Microenvironment

Yan Zhang, Alexes C. Daquinag, Felipe Amaya-Manzanares, Olga Sirin, Chieh Tseng, and Mikhail G. Kolonin

Epidemiologic studies associate cancer with obesity, but the pathophysiologic connections remain obscure. In this study, we show that obesity facilitates tumor growth in mice irrespective of concurrent diet, suggesting a direct effect of excess white adipose tissue (WAT). When transplanted into mice, adipose stromal cells (ASC) can serve as perivascular adipocyte progenitors that promote tumor growth, perhaps helping explain the obesity–cancer link. In developing this hypothesis, we showed that ASCs are expanded in obesity and that they traffic from endogenous WAT to tumors in several mouse models of cancer. Strikingly, a comparison of circulating and tumor-infiltrating cell populations in lean, and obese mice revealed that cancer induces a six-fold increase of ASC frequency in the systemic circulation. We obtained evidence that ASCs mobilized in this way can be recruited into tumors, where they can be incorporated into blood vessels as pericytes and they can differentiate into adipocytes in an obesity-dependent manner. Extending this evidence, we found that increased tumor vascularization (reflected by changes in tumor vascular morphology and a two-fold increase in vascular density) was associated with intratumoral adipocytes and elevated proliferation of neighboring malignant cells. Taken together, our results suggest that ASCs recruited from endogenous adipose tissue can be recruited by tumors to potentiate the supportive properties of the tumor microenvironment.