High-fat diet-fed ovariectomized mice are susceptible to accelerated subcutaneous tumor growth potentially through adipose tissue inflammation, local insulin-like growth factor release, and tumor associated macrophages.
High-fat diet-fed ovariectomized mice are susceptible to accelerated subcutaneous tumor growth potentially through adipose tissue inflammation, local insulin-like growth factor release, and tumor associated macrophages.
复制标题
DOI：
10.18632/oncotarget.27832
复制
发表时间：
2020-12-08
期刊：
影响因子：
--
通讯作者：
Murphy A
中科院分区：
文献类型：
--
作者：
Bader J;Carson M;Enos R;Velazquez K;Sougiannis A;Singh U;Becker W;Nagarkatti M;Fan D;Murphy A
背景：肥胖和结直肠癌(CRC)风险之间的关系已经得到了很好的证实。这种关系在男性身上似乎比在女性身上更显著，这可能归因于性激素。然而，缺乏对照动物研究来证实这些说法和涉及的机制。材料和方法：将MC38小鼠结肠腺癌细胞接种于高脂饮食(HFD)饲养的雄性、雌性和去卵巢(OVX)雌性C57BL/6小鼠体内。结果：HFD促进肿瘤生长(主效)与代谢紊乱一致(P<；0.01)。与HFD雄性和雌性小鼠相比，HFD OVX小鼠表现出最显著的肿瘤生长(p<；0.05)，这与皮下脂肪组织的增加有关(p<；0.05)。此外，与雌性小鼠相比，HFD OVX小鼠的皮下脂肪组织库显示出更严重的巨噬细胞相关炎症(P<；0.01)，但雄性小鼠没有。来自HFD OVX皮下脂肪组织的条件培养液中的IGF-1水平高于雄性(P<；0.01)，但雌性小鼠没有。最后，与雌性小鼠相比，HFD OVX小鼠肿瘤相关巨噬细胞(TAM)中M2样基因的表达增加(P<；0.01)。结论：在缺乏卵巢激素的女性中，肥胖、脂肪特异性IGF-1、巨噬细胞相关脂肪炎症和TAMS是导致肥胖增强结直肠癌的潜在机制。
Background: The association between obesity and colorectal cancer (CRC) risk has been well established. This relationship appears to be more significant in men than in women, which may be attributable to sex hormones. However, controlled animal studies to substantiate these claims and the mechanisms involved are lacking. Materials and Methods: MC38 murine colon adenocarcinoma cells were injected subcutaneously into high-fat diet (HFD) fed male, female and ovariectomized (OVX) female C57BL/6 mice. Results: HFD increased tumor growth (main effect) that was consistent with metabolic perturbations (P < 0.01). HFD OVX mice exhibited the most significant tumor growth compared to HFD male and female mice (p < 0.05) and this was associated with increased subcutaneous adipose tissue (p < 0.05). Further, the subcutaneous adipose tissue depots within HFD OVX mice exhibited more severe macrophage associated inflammation compared to female (P < 0.01), but not male mice. Conditioned media from subcutaneous adipose tissue of HFD OVX contained higher IGF-1 levels compared to male (P < 0.01), but not female mice. Finally, HFD OVX mice had increased M2-like gene expression in their tumor-associated macrophages (TAMs) compared to female mice (P < 0.01). Conclusions: This work provides evidences suggesting adiposity, adipose specific IGF-1, macrophage associated adipose inflammation, and TAMs as potential mechanisms driving obesity-enhanced CRC in females lacking ovarian hormones.