Deep membrane proteome profiling reveals overexpression of prostate-specific membrane antigen (Psma) in high-risk human paraganglioma and pheochromocytoma, suggesting new theranostic opportunity

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F21%3A10439491" target="_blank" >RIV/00064165:_____/21:10439491 - isvavai.cz</a>

Alternative codes found

RIV/00098892:_____/21:N0000053 RIV/00216208:11110/21:10439491 RIV/61989592:15110/21:73610037

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OpsOIDJ5Uh" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OpsOIDJ5Uh</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules26216567" target="_blank" >10.3390/molecules26216567</a>

Result language

angličtina

Original language name

Deep membrane proteome profiling reveals overexpression of prostate-specific membrane antigen (Psma) in high-risk human paraganglioma and pheochromocytoma, suggesting new theranostic opportunity

Original language description

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of adrenal medulla or sympathetic or parasympathetic paraganglia, respectively. To identify new therapeutic targets, we performed a detailed membrane-focused proteomic analysis of five human paraganglioma (PGL) samples. Using the Pitchfork strategy, which combines specific enrichments of glycopeptides, hydrophobic transmembrane segments, and nonglycosylated extra-membrane peptides, we identified over 1800 integral membrane proteins (IMPs). We found 45 &quot;tumor enriched&quot; proteins, i.e., proteins identified in all five PGLs but not found in control chromaffin tissue. Among them, 18 IMPs were predicted to be localized on the cell surface, a preferred drug targeting site, including prostate-specific membrane antigen (PSMA), a well-established target for nuclear imaging and therapy of advanced prostate cancer. Using specific antibodies, we verified PSMA expression in 22 well-characterized human PPGL samples. Compared to control chromaffin tissue, PSMA was markedly overexpressed in high-risk PPGLs belonging to the established Cluster 1, which is characterized by worse clinical outcomes, pseudohypoxia, multiplicity, recurrence, and metastasis, specifically including SDHB, VHL, and EPAS1 mutations. Using immunohistochemistry, we localized PSMA expression to tumor vasculature. Our study provides the first direct evidence of PSMA overexpression in PPGLs which could translate to therapeutic and diagnostic applications of anti-PSMA radio-conjugates in high-risk PPGLs.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10600 - Biological sciences

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecules

ISSN

1420-3049

e-ISSN

—

Volume of the periodical

26

Issue of the periodical within the volume

21

Country of publishing house

CH - SWITZERLAND

Number of pages

17

Pages from-to

6567

UT code for WoS article

000806934100001

EID of the result in the Scopus database

2-s2.0-85118394512