Identification of alternative protein targets of glutamate-ureido-lysine associated with PSMA tracer uptake in prostate cancer cells.
Animals
Antigens, Surface
/ chemistry
Binding Sites
Cell Cycle Proteins
/ genetics
Disease Models, Animal
Disease Progression
Fluorescent Antibody Technique
Fluorescent Dyes
/ chemical synthesis
Gene Expression
Glutamate Carboxypeptidase II
/ chemistry
Glutamates
/ chemistry
Humans
Immunohistochemistry
Lysine
/ chemistry
Male
Mice
Models, Molecular
Molecular Conformation
Molecular Imaging
/ methods
Molecular Probes
/ chemistry
Prostatic Neoplasms
/ diagnosis
Protein Binding
Receptors, Kainic Acid
/ genetics
Structure-Activity Relationship
Urea
/ analogs & derivatives
PET
PSMA
glutamate-ureido-lysine
molecular imaging
prostate cancer
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
25 01 2022
25 01 2022
Historique:
accepted:
17
11
2021
entrez:
22
1
2022
pubmed:
23
1
2022
medline:
1
3
2022
Statut:
ppublish
Résumé
Prostate-specific membrane antigen (PSMA) is highly overexpressed in most prostate cancers and is clinically visualized using PSMA-specific probes incorporating glutamate-ureido-lysine (GUL). PSMA is effectively absent from certain high-mortality, treatment-resistant subsets of prostate cancers, such as neuroendocrine prostate cancer (NEPC); however, GUL-based PSMA tracers are still reported to have the potential to identify NEPC metastatic tumors. These probes may bind unknown proteins associated with PSMA-suppressed cancers. We have identified the up-regulation of PSMA-like aminopeptidase NAALADaseL and the metabotropic glutamate receptors (mGluRs) in PSMA-suppressed prostate cancers and find that their expression levels inversely correlate with PSMA expression and are associated with GUL-based radiotracer uptake. Furthermore, we identify that NAALADaseL and mGluR expression correlates with a unique cell cycle signature. This provides an opportunity for the future study of the biology of NEPC and potential therapeutic directions. Computationally predicting that GUL-based probes bind well to these targets, we designed and synthesized a fluorescent PSMA tracer to investigate these proteins in vitro, where it shows excellent affinity for PSMA, NAALADaseL, and specific mGluRs associated with poor prognosis.
Identifiants
pubmed: 35064078
pii: 2025710119
doi: 10.1073/pnas.2025710119
pmc: PMC8795759
pii:
doi:
Substances chimiques
Antigens, Surface
0
Cell Cycle Proteins
0
Fluorescent Dyes
0
Glutamates
0
Molecular Probes
0
Receptors, Kainic Acid
0
Urea
8W8T17847W
FOLH1 protein, human
EC 3.4.17.21
Glutamate Carboxypeptidase II
EC 3.4.17.21
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA212379
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA257811
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
Endocr Relat Cancer. 2006 Mar;13(1):181-95
pubmed: 16601287
Cancer Cell. 2010 Jul 13;18(1):11-22
pubmed: 20579941
J Med Chem. 2020 Oct 8;63(19):10897-10907
pubmed: 32852205
Eur Urol. 2019 Oct;76(4):469-478
pubmed: 31345636
Structure. 2012 Apr 4;20(4):718-28
pubmed: 22483118
Bioorg Med Chem. 2007 Dec 1;15(23):7434-43
pubmed: 17869524
Clin Genitourin Cancer. 2021 Aug;19(4):e200-e205
pubmed: 33678552
Pharmaceuticals (Basel). 2017 Sep 27;10(4):
pubmed: 28953234
Bioorg Med Chem Lett. 2015 Nov 15;25(22):5232-6
pubmed: 26459214
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
J Nucl Med. 2020 Jun;61(6):904-910
pubmed: 31806771
Cancer Cell. 2017 Oct 9;32(4):474-489.e6
pubmed: 29017058
Front Oncol. 2018 Dec 20;8:623
pubmed: 30619757
Nucl Med Mol Imaging. 2017 Sep;51(3):202-211
pubmed: 28878845
Endocr Relat Cancer. 2018 Oct 1;26(2):131-146
pubmed: 30400059
EBioMedicine. 2017 Mar;17:5-6
pubmed: 28286059
J Nucl Med. 2019 Jan;60(1):71-78
pubmed: 30237214
J Med Chem. 2008 Dec 25;51(24):7737-43
pubmed: 19053759
Prostate. 2014 Aug;74(11):1153-9
pubmed: 24913988
Bioorg Med Chem. 2019 Jan 15;27(2):255-264
pubmed: 30552009
J Med Chem. 2004 Mar 25;47(7):1739-49
pubmed: 15027865
Bioconjug Chem. 2012 Apr 18;23(4):688-97
pubmed: 22369515
Clin Cancer Res. 2020 Jun 15;26(12):2946-2955
pubmed: 31932492
J Exp Med. 2018 Jan 2;215(1):159-175
pubmed: 29141866
Am J Physiol Renal Physiol. 2020 Mar 1;318(3):F809-F816
pubmed: 32068457
Pharmaceuticals (Basel). 2020 Jan 13;13(1):
pubmed: 31940969
J Med Chem. 2016 May 26;59(10):4539-50
pubmed: 27074627
J Nucl Med. 2020 Jan;61(1):58-61
pubmed: 31201249
Cell Rep. 2015 Aug 11;12(6):922-36
pubmed: 26235627
Neurochem Res. 2020 Jun;45(6):1256-1267
pubmed: 31749072
Mol Pharm. 2019 Jun 3;16(6):2590-2604
pubmed: 31002252
Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11428-11436
pubmed: 31061129
Nat Struct Mol Biol. 2015 May;22(5):362-9
pubmed: 25895059
J Nucl Med. 2018 Apr;59(4):639-645
pubmed: 29191856
Nat Rev Urol. 2016 Apr;13(4):226-35
pubmed: 26902337
CA Cancer J Clin. 2021 Jan;71(1):7-33
pubmed: 33433946
J Biol Chem. 1999 Mar 26;274(13):8470-83
pubmed: 10085079
EMBO J. 2006 Mar 22;25(6):1375-84
pubmed: 16467855
Nat Rev Urol. 2020 Feb;17(2):107-118
pubmed: 31937920
Cell Mol Life Sci. 2002 Aug;59(8):1317-26
pubmed: 12363035
Curr Med Chem. 2012;19(9):1300-9
pubmed: 22304708
Eur J Nucl Med Mol Imaging. 2021 Feb;48(2):501-508
pubmed: 32808077
Eur Urol Oncol. 2019 Nov;2(6):670-676
pubmed: 31412006
Nat Med. 2016 Mar;22(3):298-305
pubmed: 26855148
Curr Oncol Rep. 2021 Jan 12;23(2):15
pubmed: 33433737
Cell Syst. 2018 Nov 28;7(5):556-561.e3
pubmed: 30447998
J Nucl Med. 2020 Apr;61(4):527-532
pubmed: 31562225
Nucl Med Biol. 2015 Oct;42(10):780-7
pubmed: 26169882
Clin Cancer Res. 2021 Jun 1;27(11):3017-3027
pubmed: 33727260
J Drug Target. 2016 Sep;24(8):679-93
pubmed: 26887438
J Nucl Med. 2020 Nov;61(11):1602-1606
pubmed: 32169910
J Am Chem Soc. 2010 Sep 15;132(36):12711-6
pubmed: 20726553