Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
Endocr Rev. 2023 Nov 9;44(6):961-974. doi: 10.1210/endrev/bnad015.
Adipose tissue is the largest endocrine organ and an accepted contributor to overall energy homeostasis. There is strong evidence linking increased adiposity to the development of 13 types of cancer. With increased adiposity comes metabolic dysfunction and insulin resistance, and increased systemic insulin and glucose support the growth of many cancers, including those of the colon and endometrium. There is also an important direct crosstalk between adipose tissue and various organs. For instance, the healthy development and function of the mammary gland, as well as the development, growth, and progression of breast cancer, are heavily impacted by the breast adipose tissue in which breast epithelial cells are embedded. Cells of the adipose tissue are responsive to external stimuli, including overfeeding, leading to remodeling and important changes in the secretion of factors known to drive the development and growth of cancers. Loss of factors like adiponectin and increased production of leptin, endotrophin, steroid hormones, and inflammatory mediators have been determined to be important mediators of the obesity-cancer link. Obesity is also associated with a structural remodeling of the adipose tissue, including increased localized fibrosis and disrupted angiogenesis that contribute to the development and progression of cancers. Furthermore, tumor cells feed off the adipose tissue, where increased lipolysis within adipocytes leads to the release of fatty acids and stromal cell aerobic glycolysis leading to the increased production of lactate. Both have been hypothesized to support the higher energetic demands of cancer cells. Here, we aim to provide an update on the state of the literature revolving around the role of the adipose tissue in cancer initiation and progression.
脂肪组织是最大的内分泌器官，被认为是整体能量平衡的贡献者。有强有力的证据表明，肥胖与 13 种癌症的发展有关。随着肥胖的增加，会出现代谢功能障碍和胰岛素抵抗，而全身胰岛素和葡萄糖的增加则支持许多癌症的生长，包括结肠癌和子宫内膜癌。脂肪组织与各种器官之间也存在着重要的直接相互作用。例如，乳腺的健康发育和功能，以及乳腺癌的发展、生长和进展，都受到乳腺脂肪组织的强烈影响，乳腺上皮细胞嵌入其中。脂肪组织中的细胞对外界刺激有反应，包括过度喂养，导致细胞重塑，并对已知驱动癌症发展和生长的因素的分泌产生重要变化。已经确定，诸如脂联素的损失和瘦素、内毒素、甾体激素和炎症介质的产生增加等因素是肥胖与癌症关联的重要介质。肥胖还与脂肪组织的结构重塑有关，包括局部纤维化增加和血管生成中断，这有助于癌症的发展和进展。此外，肿瘤细胞依赖脂肪组织，脂肪细胞内的脂肪分解增加导致脂肪酸的释放，基质细胞有氧糖酵解导致乳酸的产生增加。这两者都被假设为支持癌细胞更高的能量需求。在这里，我们旨在提供关于脂肪组织在癌症发生和发展中的作用的文献综述的最新情况。
