Deep Membrane Proteome Profiling Reveals Overexpression of Prostate-Specific Membrane Antigen (PSMA) in High-Risk Human Paraganglioma and Pheochromocytoma, Suggesting New Theranostic Opportunity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00098892%3A_____%2F21%3AN0000053" target="_blank" >RIV/00098892:_____/21:N0000053 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/21:10439491 RIV/00064165:_____/21:10439491 RIV/61989592:15110/21:73610037

Výsledek na webu

<a href="https://www.mdpi.com/1420-3049/26/21/6567/htm" target="_blank" >https://www.mdpi.com/1420-3049/26/21/6567/htm</a>

DOI - Digital Object Identifier

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

Jazyk výsledku

angličtina

Název v původním jazyce

Deep Membrane Proteome Profiling Reveals Overexpression of Prostate-Specific Membrane Antigen (PSMA) in High-Risk Human Paraganglioma and Pheochromocytoma, Suggesting New Theranostic Opportunity

Popis výsledku v původním jazyce

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 “tumor enriched” 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.

Název v anglickém jazyce

Deep Membrane Proteome Profiling Reveals Overexpression of Prostate-Specific Membrane Antigen (PSMA) in High-Risk Human Paraganglioma and Pheochromocytoma, Suggesting New Theranostic Opportunity

Popis výsledku anglicky

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 “tumor enriched” 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Molecules

ISSN

1420-3049

e-ISSN

1420-3049

Svazek periodika

26

Číslo periodika v rámci svazku

21

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

17

Strana od-do

6567

Kód UT WoS článku

000806934100001

EID výsledku v databázi Scopus

2-s2.0-85118394512