Abstract:
Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-β family, is a stress-induced cytokine. Under normal circumstances, the expression of GDF15 is low in most tissues. It is highly expressed during tissue injury, inflammation, oxidative stress and cancer. GDF15 has been established as a biomarker in patients with cancer, and is associated with cancer cachexia (CC) and poor survival. CC is a multifactorial metabolic disorder characterized by severe muscle and adipose tissue atrophy, loss of appetite, anemia and bone loss. Cachexia leads to reductions in quality of life and tolerance to anticancer therapy, and results in a poor prognosis in cancer patients. Dysregulated GDF15 levels have been discovered in patients with CC and animal models, where they have been found to be involved in anorexia and weight loss. Although studies have suggested that GDF15 mediates anorexia and weight loss in CC through its neuroreceptor, glial cell-lineage neurotrophic factor family receptor α-like, the effects of GDF15 on CC and the potential regulatory mechanisms require further elucidation. In the present review, the characteristics of GDF15 and its roles and molecular mechanisms in CC are elaborated. The targeting of GDF15 as a potential therapeutic strategy for CC is also discussed.
摘要:
生长分化因子15(GDF15),转化生长因子-β家族的成员,是应激诱导的细胞因子。在正常情况下,GDF15在大多数组织中表达较低。它在组织损伤期间高表达,炎症,氧化应激和癌症。GDF15已被确立为癌症患者的生物标志物,与癌症恶病质(CC)和低生存率有关。CC是一种多因素代谢紊乱,其特征是严重的肌肉和脂肪组织萎缩,食欲不振,贫血和骨质流失。恶病质导致生活质量和对抗癌治疗的耐受性下降,并导致癌症患者预后不良。在CC患者和动物模型中发现GDF15水平失调,在那里他们被发现与厌食症和体重减轻有关。尽管研究表明GDF15通过其神经受体介导CC中的厌食症和体重减轻,神经胶质细胞系神经营养因子家族受体α样,GDF15对CC的影响和潜在的调控机制需要进一步阐明.在本次审查中,阐述了GDF15的特性及其在CC中的作用和分子机制。还讨论了GDF15作为CC的潜在治疗策略的靶向。