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We have provided evidence that small extracellular vesicles released by PrCa cells and containing the \u03b1V\u03b23 integrin promote neuroendocrine differentiation of PrCa<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>. Here, we examined \u03b1V\u03b23 integrin expression in three murine models carrying a deletion of<jats:italic>PTEN<\/jats:italic>(SKO),<jats:italic>PTEN<\/jats:italic>and<jats:italic>RB1<\/jats:italic>(DKO), or<jats:italic>PTEN<\/jats:italic>,<jats:italic>RB1<\/jats:italic>and<jats:italic>TRP53<\/jats:italic>(TKO) genes in the prostatic epithelium; of these three models, the DKO and TKO tumors develop NEPrCa with a gene signature comparable to those of human NEPrCa. Immunostaining analysis of SKO, DKO and TKO tumors shows that \u03b1V\u03b23 integrin expression is increased in DKO and TKO primary tumors and metastatic lesions, but absent in SKO primary tumors. On the other hand, SKO tumors show higher levels of a different \u03b1V integrin, \u03b1V\u03b26, as compared to DKO and TKO tumors. These results are confirmed by RNA-sequencing analysis. Moreover, TRAMP mice, which carry NEPrCa and adenocarcinoma of the prostate, also have increased levels of \u03b1V\u03b23 in their NEPrCa primary tumors. In contrast, the \u03b1V\u03b26 integrin is only detectable in the adenocarcinoma areas. Finally, analysis of 42 LuCaP patient-derived xenografts and primary adenocarcinoma samples shows a positive correlation between \u03b1V\u03b23, but not \u03b1V\u03b26, and the neuronal marker synaptophysin; it also demonstrates that \u03b1V\u03b23 is absent in prostatic adenocarcinomas. In summary, we demonstrate that \u03b1V\u03b23 integrin is upregulated in NEPrCa primary and metastatic lesions; in contrast, the \u03b1V\u03b26 integrin is confined to adenocarcinoma of the prostate. Our findings suggest that the \u03b1V\u03b23 integrin, but not \u03b1V\u03b26, may promote a shift in lineage plasticity towards a NE phenotype and might serve as an informative biomarker for the early detection of NE differentiation in prostate cancer.<\/jats:p>","DOI":"10.1371\/journal.pone.0244985","type":"journal-article","created":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T22:40:58Z","timestamp":1611355258000},"page":"e0244985","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Differential expression of \u03b1V\u03b23 and \u03b1V\u03b26 integrins in prostate cancer progression"],"prefix":"10.1371","volume":"16","author":[{"given":"Fabio","family":"Quaglia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv 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