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一项新的研究表明，肿瘤细胞释放因子进入血液，抑制受损肌肉纤维的修复，导致癌症条件下的肌肉流失。癌症条件下的肌肉流失也被称为癌性恶病质，在多种类型的癌症患者中存在，此类症状导致危及生命的体重和肌肉质量损失，并负责四分之一的癌症死亡。目前，还没有治疗手段。
新研究指出了新的战略和新的药物靶点来治疗癌症恶病质。这项研究结果发表在Journal of Clinical Investigation杂志上。
研究人员关注于肌肉干细胞，它也被称为卫星细胞。这些细胞与肌纤维有关，是修复受损纤维必不可少的细胞。通常情况下，肌纤维的损坏会导致这些干细胞的增殖，分化成成熟的肌肉细胞。然后，这些肌肉细胞与受损部位周围纤维融合限制肌肉萎缩。研究人员说，这一过程在癌症恶病质中被阻断。
新研究表明，虽然肌肉干细胞被激活，但在恶病质中，肿瘤细胞释放的因素阻断肌肉干细胞分化成肌肉细胞，让他们无法修复受损肌纤维。因此，寻找到能克服阻断和允许肌肉干细胞分化的药物，有可能恢复肌肉质量，提高癌症恶病质患者的生活质量。
在这项研究中，Guttridge和他的同事们使用动物模型和恶病质胰腺癌患者组织，发现了肌肉微环境中有助于癌症恶病质的因素。主要调查结果包括：恶病质与肿瘤引起的骨骼肌细胞损坏和肿瘤诱导的肌肉干细胞增殖有关；过度表达的肌肉干细胞因子PAX7会阻止细胞的分化能力，并促进癌症引起的肌肉消瘦；PAX7的过度表达受NF-κB控制，NF-κB已被证明在癌症中扮演多重角色；恶病质中，NF-κB导致PAX7的表达下降，这反过来又损害肌肉祖细胞的分化，促进肌肉萎缩；由于其组织特异性，抑制PAX7可能是一个潜在的癌症恶病质治疗手段。（生物谷Bioon.com）
NF-κB-mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia.
He WA, Berardi E, Cardillo VM, Acharyya S, Aulino P, Thomas-Ahner J, Wang J, Bloomston M, Muscarella P, Nau P, Shah N, Butchbach ME, Ladner K, Adamo S, Rudnicki MA, Keller C, Coletti D, Montanaro F, Guttridge DC.
Cachexia is a debilitating condition characterized by extreme skeletal muscle wasting that contributes significantly to morbidity and mortality. Efforts to elucidate the underlying mechanisms of muscle loss have predominantly focused on events intrinsic to the myofiber. In contrast, less regard has been given to potential contributory factors outside the fiber within the muscle microenvironment. In tumor-bearing mice and patients with pancreatic cancer, we found that cachexia was associated with a type of muscle damage resulting in activation of both satellite and nonsatellite muscle progenitor cells. These muscle progenitors committed to a myogenic program, but were inhibited from completing differentiation by an event linked with persistent expression of the self-renewing factor Pax7. Overexpression of Pax7 was sufficient to induce atrophy in normal muscle, while under tumor conditions, the reduction of Pax7 or exogenous addition of its downstream target, MyoD, reversed wasting by restoring cell differentiation and fusion with injured fibers. Furthermore, Pax7 was induced by serum factors from cachectic mice and patients, in an NF-κB-dependent manner, both in vitro and in vivo. Together, these results suggest that Pax7 responds to NF-κB by impairing the regenerative capacity of myogenic cells in the muscle microenvironment to drive muscle wasting in cancer.