biostudies-literatureGregory ENational Cancer InstituteNCI NIH HHSPharmaceutical Research and Manufacturers of America FoundationNational Institute of General Medical SciencesNIGMS NIH HHSArkansas Biosciences Institute45-58https://www.ebi.ac.uk/biostudies/studies/S-EPMC11950487biostudies-literatureUnknown4(1)<h4>Purpose</h4>Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related deaths, and perineural invasion (PNI), in which cancer cells infiltrate nerves, enables metastasis in most patients. PNI is largely attributed to Schwann cells (SC) that, when activated, accelerate cancer cell migration towards nerves. However, this cancer-associated reprogramming is generally under-appreciated. Additionally, tumor extracellular vesicle (EV) facilitation of cancer aggravation is well documented, but more investigation is required to better understand their role in PNI. Here, we assessed whether PDAC EVs mediate PNI via SC activation using tissue-engineered in vitro platforms and PANC-1 and HPNE human cell lines as models.<h4>Methods</h4>NanoSight, Luminex®, and proteomic-pathwIn vitro modelsPancreatic cancer extracellular vesicles stimulate Schwann cell activation and perineural invasion in vitro via IL-8/CCL2.PMC11950487P20 GM139768R24 GM137786R24GM137786R37 CA279722P20GM139768R37CA279722Powers IGriffin RJGregory EJamshidi-Parsian ASong YfalsePancreatic cancer extracellular vesicles stimulate Schwann cell activation and perineural invasion in vitro via IL-8/CCL2.<h4>Purpose</h4>Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related deaths, and perineural invasion (PNI), in which cancer cells infiltrate nerves, enables metastasis in most patients. PNI is largely attributed to Schwann cells (SC) that, when activated, accelerate cancer cell migration towards nerves. However, this cancer-associated reprogramming is generally under-appreciated. Additionally, tumor extracellular vesicle (EV) facilitation of cancer aggravation is well documented, but more investigation is required to better understand their role in PNI. Here, we assessed whether PDAC EVs mediate PNI via SC activation using tissue-engineered in vitro platforms and PANC-1 and HPNE human cell lines as models.<h4>Methods</h4>NanoSight, Luminex®, and proteomic-pathw2025-01-01T00:00:00Z2025 Feb2025-07-12T03:04:17.307Z2025-07-12T03:04:17.307ZS-EPMC119504874016020810.1007/s44164-025-00083-w