Tumor-derived MMPs regulate cachexia in a Drosophila cancer model.
William Lodge, Michael Zavortink, Sofia Golenkina, Francesca Froldi, Callum Dark, Shane Cheung, Benjamin L Parker, Ronnie Blazev, Daniel Bakopoulos, Elizabeth L Christie, Verena C Wimmer, Brigette C Duckworth, Helena E Richardson, Louise Y Cheng
Dev Cell | Published : 2021
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 b..View full abstract