Cancer-associated muscle wasting (CAW), a symptom of cancer cachexia, is associated with approximately 20% of lung cancer deaths and remains poorly characterized on a mechanistic level. Current animal models for lung cancer-associated cachexia are limited in that they (1) primarily employ flank transplantation methods, (2) have short survival times not reflective of the patient condition, and (3) are typically performed in young mice not representative of mean patient age. This study investigates a new model for lung cancer-associated cachexia that can address these issues and also implicates muscle regeneration as a contributor to CAW. We used tail vein injection as a method to introduce tumor cells that seed primarily in the lungs of mice. Body composition of tumor-bearing mice was longitudinally tracked using NMR-based, echo magnetic resonance imaging (echoMRI). These data were combined with histological and molecular assessments of skeletal muscle to provide a complete analysis of muscle wasting. In this new lung CAW model, we observed (1) progressive loss in whole body weight, (2) progressive loss of lean and fat mass, (3) a circulating cytokine/inflammatory profile similar to that seen in other models of CAW, (4) histological changes associated with muscle wasting, and (5) molecular changes in muscle that implicate suppression of muscle repair/regeneration. Finally, we show that survival can be extended without lessening CAW by titrating injected cell number. Overall, this study describes a new model of CAW that could be useful for further studies of lung cancer-associated wasting and accompanying changes in the regenerative capacity of muscle. Additionally, this model addresses many recent concerns with existing models such as immunocompetence, tumor location, and survival time.

中文翻译：

---

肺癌相关组织损失和肌肉再生破坏的新型可移植模型。


癌症相关肌肉萎缩 (CAW) 是癌症恶病质的一种症状，与大约 20% 的肺癌死亡相关，但在机制层面上仍然缺乏表征。目前肺癌相关恶病质的动物模型存在局限性，因为它们（1）主要采用侧腹移植方法，（2）存活时间短，不能反映患者状况，（3）通常在不代表成年小鼠的年轻小鼠中进行。患者平均年龄。这项研究调查了一种与肺癌相关的恶病质的新模型，该模型可以解决这些问题，并且还表明肌肉再生是 CAW 的一个促成因素。我们使用尾静脉注射作为引入主要在小鼠肺部种植的肿瘤细胞的方法。使用基于 NMR 的回声磁共振成像 (echoMRI) 纵向跟踪荷瘤小鼠的身体成分。这些数据与骨骼肌的组织学和分子评估相结合，以提供肌肉萎缩的完整分析。在这个新的肺 CAW 模型中，我们观察到 (1) 全身重量逐渐减少，(2) 瘦肉量和脂肪量逐渐减少，(3) 循环细胞因子/炎症特征与其他 CAW 模型相似，( 4）与肌肉萎缩相关的组织学变化，以及（5）肌肉中涉及肌肉修复/再生抑制的分子变化。最后，我们表明通过滴定注射细胞数量可以在不减少 CAW 的情况下延长生存期。总的来说，这项研究描述了一种新的 CAW 模型，可用于进一步研究肺癌相关的消耗以及伴随的肌肉再生能力的变化。 此外，该模型还解决了现有模型的许多最新问题，例如免疫能力、肿瘤位置和生存时间。