Cachexia, the wasting syndrome commonly observed in advanced cancer patients, accounts for up to one-third of cancer-related mortalities. We have established a Drosophila larval model of organ wasting whereby epithelial overgrowth in eye-antennal discs leads to wasting of the adipose tissue and muscles. The wasting is associated with fat-body remodeling and muscle detachment and is dependent on tumor-secreted matrix metalloproteinase 1 (Mmp1). Mmp1 can both modulate TGFβ signaling in the fat body and disrupt basement membrane (BM)/extracellular matrix (ECM) protein localization in both the fat body and the muscle. Inhibition of TGFβ signaling or Mmps in the fat body/muscle using a QF2-QUAS binary expression system rescues muscle wasting in the presence of tumor. Altogether, our study proposes that tumor-derived Mmps are central mediators of organ wasting in cancer cachexia.

恶病质是晚期癌症患者中常见的消耗综合征，占癌症相关死亡率的三分之一。我们已经建立了一个果蝇器官消瘦的幼虫模型，其中眼-触角盘中的上皮过度生长导致脂肪组织和肌肉的消瘦。消瘦与脂肪体重塑和肌肉脱离有关，并且依赖于肿瘤分泌的基质金属蛋白酶 1 (Mmp1)。Mmp1 既可以调节脂肪体中的 TGFβ 信号传导，也可以破坏脂肪体和肌肉中的基底膜 (BM)/细胞外基质 (ECM) 蛋白定位。使用 QF2-QUAS 二元表达系统抑制脂肪体/肌肉中的 TGFβ 信号或 Mmps 可挽救肿瘤存在时的肌肉萎缩。总而言之，我们的研究表明，肿瘤衍生的 Mmps 是癌症恶病质中器官消耗的中心介质。