| First Author | Quaglia F | Year | 2021 |
| Journal | PLoS One | Volume | 16 |
| Issue | 1 | Pages | e0244985 |
| PubMed ID | 33481853 | Mgi Jnum | J:300806 |
| Mgi Id | MGI:6503965 | Doi | 10.1371/journal.pone.0244985 |
| Citation | Quaglia F, et al. (2021) Differential expression of alphaVbeta3 and alphaVbeta6 integrins in prostate cancer progression. PLoS One 16(1):e0244985 |
| abstractText | Neuroendocrine prostate cancer (NEPrCa) arises de novo or after accumulation of genomic alterations in pre-existing adenocarcinoma tumors in response to androgen deprivation therapies. We have provided evidence that small extracellular vesicles released by PrCa cells and containing the alphaVbeta3 integrin promote neuroendocrine differentiation of PrCa in vivo and in vitro. Here, we examined alphaVbeta3 integrin expression in three murine models carrying a deletion of PTEN (SKO), PTEN and RB1 (DKO), or PTEN, RB1 and TRP53 (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 alphaVbeta3 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 alphaV integrin, alphaVbeta6, 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 alphaVbeta3 in their NEPrCa primary tumors. In contrast, the alphaVbeta6 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 alphaVbeta3, but not alphaVbeta6, and the neuronal marker synaptophysin; it also demonstrates that alphaVbeta3 is absent in prostatic adenocarcinomas. In summary, we demonstrate that alphaVbeta3 integrin is upregulated in NEPrCa primary and metastatic lesions; in contrast, the alphaVbeta6 integrin is confined to adenocarcinoma of the prostate. Our findings suggest that the alphaVbeta3 integrin, but not alphaVbeta6, 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. |
