Tumor-derived MMPs regulate cachexia in a Drosophila cancer model

Cachexia, the wasting syndrome commonly observed in advanced cancer patients, accounts for up to onethird 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 TGF beta 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 TGF beta 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.

Automated summary

The study established a Drosophila larval model where tumor-secreted Mmp1 was identified as a central mediator of organ wasting in cancer cachexia. Inhibition of TGF beta signaling or Mmp in the fat body/muscle rescued muscle wasting in the presence of tumor.