LncRNA profile of CAFs derived EVs
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ABSTRACT:
PROVIDER: PRJNA1104171 | ENA |
REPOSITORIES: ENA
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Project description:Perineural invasion (PNI) is a unique biological feature of pancreatic cancer and is a key cause of pancreatic cancer metastasis, recurrence and poor postoperative survival, but its mechanism is largely unclarified. Clinical sample analysis and endoscopic ultrasonographic elasticity scoring indicated that cancer-associated fibroblasts (CAFs) are closely related to the occurrence of PNI. Furthermore, CAF-derived extracellular vesicles played an extremely important role in PNI in a dorsal root ganglion (DRG) coculture model and sciatic nerve model. To explore the lncRNA packaged in CAFs EVs transmitted to PANC-1, we conducted the lncRNA profile of PAN-1 treated with CAFs derived EVs.
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Project description:Perineural invasion (PNI) is a unique biological feature of pancreatic cancer and is a key cause of pancreatic cancer metastasis, recurrence and poor postoperative survival, but its mechanism is largely unclarified. Clinical sample analysis and endoscopic ultrasonographic elasticity scoring indicated that cancer-associated fibroblasts (CAFs) are closely related to the occurrence of PNI. Furthermore, CAF-derived extracellular vesicles played an extremely important role in PNI in a dorsal root ganglion (DRG) coculture model and sciatic nerve model. To explore the lncRNA packaged in CAFs EVs, we conducted the lncRNA profile of CAFs isolated from pancreatic cancer
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Project description:Perineural invasion (PNI) is a unique biological feature of pancreatic cancer and is a key cause of pancreatic cancer metastasis, recurrence and poor postoperative survival, but its mechanism is largely unclarified. Clinical sample analysis and endoscopic ultrasonographic elasticity scoring indicated that cancer-associated fibroblasts (CAFs) are closely related to the occurrence of PNI. Furthermore, CAF-derived extracellular vesicles played an extremely important role in PNI in a dorsal root ganglion (DRG) coculture model and sciatic nerve model. Next, we demonstrated that CAFs promoted PNI via extracellular vesicle transmission of PNI-associated transcript (PIAT). To determine how CAF EVs exert its function, we performed mRNA sequencing on PANC-1 treated with CAFs-derived EVs
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Project description:While of growing interest in pancreatic cancer (PC) field, the stromal-tumor cells crosstalk lags behind in terms of biomarkers and therapeutic options improving the clinical armamentarium. Knowledge on cellular communications was drastically enhanced following the discovery of extracellular vesicles (EVs), a powerful process of intercellular exchanges. We previously described a new stromal-tumor cell crosstalk mediated by Cancer-Associated Fibroblasts (CAFs)-derived ANXA6+-EVs, supporting pancreatic cancer cell aggressiveness in hostile areas of PC. In this study, using mass spectrometry analyses to investigate CAFs-derived EVs' cargo, we report that CD9 is a key member of the ANXA6/LRP1/TSP1 complex present in PC-associated CAFs-derived ANXA6+-EVs. We determined that CD9 is expressed by PC-associated CAFs in vivo as well as in vitro following physiopathologic culture conditions. 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, we revealed CD9 expression as an independent poor-prognosis marker in human PC samples. Collectively our data highlight the key role of CD9 in CAFs-derived 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.
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