Prostate cancer sheds the αvβ3 integrin in vivo through exosomes.
Adenocarcinoma
/ blood
Adolescent
Adult
Aged
Aged, 80 and over
Animals
Antineoplastic Agents
/ pharmacology
Benzamides
Biomarkers, Tumor
/ blood
Exosomes
/ chemistry
Gene Expression
Humans
Integrin alphaVbeta3
/ blood
Male
Mice
Mice, Inbred NOD
Mice, SCID
Middle Aged
Nitriles
PC-3 Cells
Phenylthiohydantoin
/ analogs & derivatives
Prostatic Neoplasms
/ blood
Tetraspanin 29
/ blood
Tetraspanin 30
/ blood
Xenograft Model Antitumor Assays
Abiraterone acetate
Enzalutamide
Extracellular vesicles
Plasma exosomes
Prostate cancer
αvβ3 integrin
Journal
Matrix biology : journal of the International Society for Matrix Biology
ISSN: 1569-1802
Titre abrégé: Matrix Biol
Pays: Netherlands
ID NLM: 9432592
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
24
04
2018
revised:
03
08
2018
accepted:
05
08
2018
pubmed:
12
8
2018
medline:
3
8
2019
entrez:
12
8
2018
Statut:
ppublish
Résumé
The αvβ3 integrin has been shown to promote aggressive phenotypes in many types of cancers, including prostate cancer. We show that GFP-labeled αvβ3 derived from cancer cells circulates in the blood and is detected in distant lesions in NOD scid gamma (NSG) mice. We, therefore, hypothesized that αvβ3 travels through exosomes and tested its levels in pools of vesicles, which we designate extracellular vesicles highly enriched in exosomes (ExVs), and in exosomes isolated from the plasma of prostate cancer patients. Here, we show that the αvβ3 integrin is found in patient blood exosomes purified by sucrose or iodixanol density gradients. In addition, we provide evidence that the αvβ3 integrin is transferred through ExVs isolated from prostate cancer patient plasma to β3-negative recipient cells. We also demonstrate the intracellular localization of β3-GFP transferred via cancer cell-derived ExVs. We show that the ExVs present in plasma from prostate cancer patients contain higher levels of αvβ3 and CD9 as compared to plasma ExVs from age-matched subjects who are not affected by cancer. Furthermore, using PSMA antibody-bead mediated immunocapture, we show that the αvβ3 integrin is expressed in a subset of exosomes characterized by PSMA, CD9, CD63, and an epithelial-specific marker, Trop-2. Finally, we present evidence that the levels of αvβ3, CD63, and CD9 remain unaltered in ExVs isolated from the blood of prostate cancer patients treated with enzalutamide. Our results suggest that detecting exosomal αvβ3 integrin in prostate cancer patients could be a clinically useful and non-invasive biomarker to follow prostate cancer progression. Moreover, the ability of αvβ3 integrin to be transferred from ExVs to recipient cells provides a strong rationale for further investigating the role of αvβ3 integrin in the pathogenesis of prostate cancer and as a potential therapeutic target.
Identifiants
pubmed: 30098419
pii: S0945-053X(18)30146-X
doi: 10.1016/j.matbio.2018.08.004
pmc: PMC6541230
mid: NIHMS1024687
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Benzamides
0
Biomarkers, Tumor
0
CD63 protein, human
0
CD9 protein, human
0
Integrin alphaVbeta3
0
Nitriles
0
Tetraspanin 29
0
Tetraspanin 30
0
Phenylthiohydantoin
2010-15-3
enzalutamide
93T0T9GKNU
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Pagination
41-57Subventions
Organisme : NCI NIH HHS
ID : P01 CA140043
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA039481
Pays : United States
Organisme : NIH HHS
ID : S10 OD012406
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA109874
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA157372
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA056036
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA224769
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA047282
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.
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