Calix[6]arene dismantles extracellular vesicle biogenesis and metalloproteinases that support pancreatic cancer hallmarks

Cell Signal. 2024 Apr 9:111174. doi: 10.1016/j.cellsig.2024.111174. Online ahead of print.ABSTRACTMany challenges are faced in pancreatic cancer treatment due to late diagnosis and poor prognosis because of high recurrence and metastasis. Extracellular vesicles (EVs) and matrix metalloproteinases (MMPs), besides acting in intercellular communication, are key players in the cancer cell plasticity responsible for initiating metastasis. Therefore, these entities provide valuable targets for the development of better treatments. In this context, this study aimed to evaluate the potential of calix[6]arene to disturb the release of EVs and the activity of MMPs in pancreatic cancer cells. We found a correlation between the endocytic-associated mediators and the prognosis of pancreatic cancer patients. We observed a more active EV machinery in the pancreatic cancer cell line PANC-1, which was reduced three-fold by treatment with calix[6]arene at subtoxic concentration (5 μM; p 〈0,001). We observed the modulation of 186 microRNAs (164 miRNAs upregulated and 22 miRNAs downregulated) upon calix[6]arene treatment. Interestingly, some of them as miR-4443 and miR-3909, regulates genes HIF1A e KIF13A that are well known to play a role in transport of vesicles. Furthermore, Calix[6]arene downmodulated matrix metalloproteinases (MMPs) -2 and - 9 and disturbed the viability of pancreatic organoids which recapitulate the cellular heterogeneity, structure, and functions of primary tissues. Ou...
Source: Cellular Signalling - Category: Cytology Authors: Source Type: research