Aberrant integrin αv and α5 expression in prostate adenocarcinomas and bone-metastases is consistent with a bone-colonizing phenotype.
Transl Androl Urol
; 9(4): 1630-1638, 2020 Aug.
Article
em En
| MEDLINE
| ID: mdl-32944524
ABSTRACT
BACKGROUND:
Collaborative signaling between fibronectin-binding αv and α5 integrins has been implicated in the lethal dissemination of prostate cancer in the bone-metastatic niche, the major source of morbidity and mortality in the disease.METHODS:
We assessed the frequency and pattern of expression of these integrins in primary high-grade adenocarcinomas and bone metastases compared to the physiological gland. Formalin-fixed paraffin-embedded (FFPE) radical prostatectomy (RP) samples (n=25) containing ≥ Gleason grade 4 cancer and decalcified surgical or diagnostic bone metastatic samples from 10 patients were stained for integrin αv (ITGAV) and integrin α5 (ITGA5) expression. Antibody optimization and antigen-retrieval was performed beforehand.RESULTS:
ITGAV was exclusively expressed in the basal layer of physiological prostate glands whereas αv expression was invariably recapitulated in the malignant gland and bone metastases (100%) in multiple distinct patterns epithelial membranous, basilar/luminal membranous, punctate cytoplasmic, intense foci as single cells or clusters, and rim stromal layers. The luminal/basilar layer of ITGAV expression was striking in cribriform carcinomas, suggestive of a role in molecular pathogenesis. ITGA5 infrequently highlighted the basal layer of the physiological gland, was absent in primary adenocarcinoma, but was expressed with ITGAV exclusively in bone metastases (71%).CONCLUSIONS:
We conclude that ITGAV expression is aberrantly expressed in high frequency in high-grade prostatic adenocarcinomas in patterns suggestive of recapitulated basal cell functions, consistent with a stem-regulatory role that has been proposed. Co-expression and enrichment of αv and α5 in osseous metastases supports their proposed collaborative role in colonization of the bone microenvironment and as candidate targets for therapy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Transl Androl Urol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos