Adipose tissue and adipocytes support tumorigenesis and metastasis.
Adipose tissue and adipocytes support tumorigenesis and metastasis.
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DOI：
10.1016/j.bbalip.2013.02.010
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Lengyel E
中科院分区：
文献类型：
--
作者：
Nieman KM;Romero IL;Van Houten B;Lengyel E
脂肪组织主要通过两种方式影响肿瘤的发展。首先，肥胖者患某些癌症(子宫内膜癌、食道癌和肾癌)的风险更高。然而，发生其他癌症(黑色素瘤、直肠癌和卵巢癌)的风险不会因体重而改变。在肥胖症中，肥大的脂肪组织库以低度炎症状态为特征。在这种激活状态下，脂肪细胞和炎症细胞分泌脂肪因子和细胞因子，这是已知的促进肿瘤发展的因素。此外，脂肪细胞介导的雄激素向雌激素的转化特别有助于子宫内膜癌的发展，这显示出瘦人和肥胖者之间的相对风险最大(6.3倍)。其次，许多类型的肿瘤(胃、乳腺、结肠、肾和卵巢)生长在脂肪组织的解剖附近。在与癌细胞的相互作用中，脂肪细胞去分化为前脂肪细胞或被重新编程为癌症相关脂肪细胞(CAA)。CAA分泌脂肪因子，刺激肿瘤细胞的黏附、迁移和侵袭。癌细胞和CAA也经历代谢产物的动态交换。具体地说，CAA通过脂肪分解释放脂肪酸，然后这些脂肪酸被转移到癌细胞，并通过β氧化用于能量生产。脂肪细胞在肿瘤微环境中的丰富可获得性支持肿瘤的进展和不受控制的生长。鉴于脂肪细胞是癌细胞脂肪因子和能量的主要来源，了解癌细胞和脂肪细胞之间代谢共生的机制应该会揭示新的治疗可能性。
Adipose tissue influences tumor development in two major ways. First, obese individuals have a higher risk of developing certain cancers (endometrial, esophageal, and renal cell cancer). However, the risk of developing other cancers (melanoma, rectal, and ovarian) is not altered by body mass. In obesity, hypertrophied adipose tissue depots are characterized by a state of low grade inflammation. In this activated state, adipocytes and inflammatory cells secrete adipokines and cytokines which are known to promote tumor development. In addition, the adipocyte mediated conversion of androgens to estrogen specifically contributes to the development of endometrial cancer, which shows the greatest relative risk (6.3-fold) increase between lean and obese individuals. Second, many tumor types (gastric, breast, colon, renal, and ovarian) grow in the anatomical vicinity of adipose tissue. During their interaction with cancer cells, adipocytes dedifferentiate into pre-adipocytes or are reprogrammed into cancer-associated adipocytes (CAA). CAA secrete adipokines which stimulate the adhesion, migration, and invasion of tumor cells. Cancer cells and CAA also undergo a dynamic exchange of metabolites. Specifically, CAA release fatty acids through lipolysis which are then transferred to cancer cells and used for energy production through β-oxidation. The abundant availability of lipids from adipocytes in the tumor microenvironment supports tumor progression and uncontrolled growth. Given that adipocytes are a major source of adipokines and energy for the cancer cell, understanding the mechanisms of metabolic symbiosis between cancer cells and adipocytes should reveal new therapeutic possibilities.
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