Department of Molecular Biotechnology and Health Science, Molecular Biotechnology Center, University of Torino, Torino, Italy.
Department of Translational Medicine, Istituto Interuniversitario di Miologia (IIM), University of Piemonte Orientale, Novara, Italy.
Oxid Med Cell Longev. 2018 Feb 26;2018:6419805. doi: 10.1155/2018/6419805. eCollection 2018.
Cancer cachexia is a devastating syndrome occurring in the majority of terminally ill cancer patients. Notably, skeletal muscle atrophy is a consistent feature affecting the quality of life and prognosis. To date, limited therapeutic options are available, and research in the field is hampered by the lack of satisfactory models to study the complexity of wasting in cachexia-inducing tumors, such as pancreatic cancer. Moreover, currently used models are characterized by an explosive cachexia with a lethal wasting within few days, while pancreatic cancer patients might experience alterations long before the onset of overt wasting. In this work, we established and characterized a slow-paced model of pancreatic cancer-induced muscle wasting that promotes efficient muscular wasting and . Treatment with conditioned media from pancreatic cancer cells led to the induction of atrophy , while tumor-bearing mice presented a clear reduction in muscle mass and functionality. Intriguingly, several metabolic alterations in tumor-bearing mice were identified, paving the way for therapeutic interventions with drugs targeting metabolism.
癌症恶病质是一种严重的综合征，发生于大多数晚期癌症患者中。值得注意的是，骨骼肌萎缩是一个一致的特征，影响生活质量和预后。迄今为止，可用的治疗选择有限，并且该领域的研究受到缺乏令人满意的模型来研究诱导肿瘤恶病质的复杂性的阻碍，例如胰腺癌。此外，目前使用的模型的特点是在几天内出现爆发性恶病质和致命性消耗，而胰腺癌患者在明显消耗之前可能会经历改变。在这项工作中，我们建立并表征了一种缓慢进展的胰腺癌诱导肌肉消耗模型，该模型促进了有效的肌肉消耗和萎缩。用胰腺癌细胞的条件培养基处理可导致萎缩的诱导，而荷瘤小鼠的肌肉质量和功能明显减少。有趣的是，在荷瘤小鼠中鉴定出了几种代谢改变，为针对代谢的药物治疗干预铺平了道路。
