Obesity promotes the expansion of metastasis-initiating cells in breast cancer.
Obesity promotes the expansion of metastasis-initiating cells in breast cancer.
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DOI：
10.1186/s13058-018-1029-4
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发表时间：
2018-09-04
期刊：
影响因子：
--
通讯作者：
Santamaria-Martínez A
中科院分区：
文献类型：
--
作者：
Bousquenaud M;Fico F;Solinas G;Rüegg C;Santamaria-Martínez A
肥胖是乳腺癌预后不良的一个强有力的预测因子，尤其是绝经后妇女。特别是，肥胖患者的肿瘤倾向于播下更远处转移的种子，尽管这种观察背后的生物学仍然知之甚少。为了阐明肥胖微环境对转移扩散的影响，我们切除卵巢的C57BL/6 J雌性小鼠，分别饲喂常规饮食（RD）和高脂饮食（HFD），建立绝经后饮食诱导的肥胖模型。然后我们研究了Py230和EO771移植物的肿瘤进展到转移。采用流式细胞术、qPCR、免疫组织化学（IHC）和western blot对RD和HFD肿瘤及其周围脂肪组织进行分析和表型分析。通过将RD和HFD肿瘤细胞交叉移植到其他RD和HFD小鼠体内，评估微环境对肿瘤细胞的影响。当比较两个变量时，使用unpaired Student t检验对结果进行分析，否则我们使用单向或双向方差分析。用相关系数计算两个变量之间的关系。我们的研究结果表明，肥胖小鼠的肿瘤生长速度更快，血管化程度更低，缺氧程度更高，级别更高，富含CD11b+Ly6G+中性粒细胞。总的来说，这有利于诱导上皮细胞到间质细胞的转变和向低claudio乳腺癌的进展，claudio -low乳腺癌是一种富含癌症干细胞的三阴性乳腺癌亚型。有趣的是，在RD小鼠中移植hfd来源的肿瘤细胞可促进肿瘤生长和肺转移形成。这些数据表明，肥胖的促转移作用是由原发肿瘤中的肿瘤细胞获得的，独立于继发部位的微环境。绝经后肥胖对原发性乳腺癌肿瘤的影响ᅟ本文的在线版本（10.1186/s13058-018-1029-4）包含补充材料，授权用户可获得。
Obesity is a strong predictor of poor prognosis in breast cancer, especially in postmenopausal women. In particular, tumors in obese patients tend to seed more distant metastases, although the biology behind this observation remains poorly understood. To elucidate the effects of the obese microenvironment on metastatic spread, we ovariectomized C57BL/6 J female mice and fed them either a regular diet (RD) or a high-fat diet (HFD) to generate a postmenopausal diet-induced obesity model. We then studied tumor progression to metastasis of Py230 and EO771 grafts. We analyzed and phenotyped the RD and HFD tumors and the surrounding adipose tissue by flow cytometry, qPCR, immunohistochemistry (IHC) and western blot. The influence of the microenvironment on tumor cells was assessed by performing cross-transplantation of RD and HFD tumor cells into other RD and HFD mice. The results were analyzed using the unpaired Student t test when comparing two variables, otherwise we used one-way or two-way analysis of variance. The relationship between two variables was calculated using correlation coefficients. Our results show that tumors in obese mice grow faster, are also less vascularized, more hypoxic, of higher grade and enriched in CD11b+Ly6G+ neutrophils. Collectively, this favors induction of the epithelial-to-mesenchymal transition and progression to claudin-low breast cancer, a subtype of triple-negative breast cancer that is enriched in cancer stem cells. Interestingly, transplanting HFD-derived tumor cells in RD mice transfers enhanced tumor growth and lung metastasis formation. These data indicate that a pro-metastatic effect of obesity is acquired by the tumor cells in the primary tumor independently of the microenvironment of the secondary site. Effects of postmenopausal obesity on primary breast cancer tumoursᅟ The online version of this article (10.1186/s13058-018-1029-4) contains supplementary material, which is available to authorized users.
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影响因子：
64.5
作者：
Lee YS;Kim JW;Osborne O;Oh DY;Sasik R;Schenk S;Chen A;Chung H;Murphy A;Watkins SM;Quehenberger O;Johnson RS;Olefsky JM
通讯作者：
Olefsky JM
巨噬细胞的局部扩散有助于与肥胖相关的脂肪组织炎症。
影响因子：
29
作者：
Amano SU;Cohen JL;Vangala P;Tencerova M;Nicoloro SM;Yawe JC;Shen Y;Czech MP;Aouadi M
通讯作者：
Aouadi M
影响因子：
9.7
作者：
Biswas, Tanuka;Gu, Xiang;Yang, Junhua;Ellies, Lesley G.;Sun, Lu-Zhe
通讯作者：
Sun, Lu-Zhe
DOI：
10.1038/nri3071
发表时间：
2011-10-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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影响因子：
8.4
作者：
Biganzoli, Elia;Desmedt, Christine;Demicheli, Romano
通讯作者：
Demicheli, Romano