New strategy targeting stroma/tumor cell crosstalk to treat a cancer

In this study, the Inventors report that CD9 is a key component of PC-associated CAFsderived ANXA6+-EVs. They determined that CD9 is expressed by PC-associated CAFs in vitro as well as in vivo. Targeting CD9 impaired CAFs-derived ANXA6+-EVs uptake by pancreatic cancer cells, which consequently decreases their migratory abilities. Signaling pathway arrays highlighted p38/MAPK as activated in pancreatic cancer cells following CAFs-derived ANXA6+/CD9+-EVs uptake. The use of CD9 blocking antibody, p38 siRNA or chemical inhibitors impaired pancreatic cancer cells abilities following incubation with CAFs-derived ANXA6+/CD9+-EVs. Finally, they revealed CD9 expression as an independent poor-prognosis marker in human PC samples. Collectively their data highlight the key role of CD9 in CAFs erived ANXA6+-EVs internalization by pancreatic cancer cells and the consequent, and mandatory, activation of p38/MAPK pathway to foster their migratory abilities. Measuring the oncogenic CAFs-derived ANXA6+/CD9+-EVs then limiting their action on pancreatic cancer cells abilities might be a promising option for PC stratification and treatment.

Sci Signal. 2022 Aug 2;15(745):eabg8191. doi: 10.1126/scisignal.abg8191. Epub 2022 Aug 2.

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