Exosomes released by imatinib‑resistant K562 cells contain specific membrane markers, IFITM3, CD146 and CD36 and increase the survival of imatinib‑sensitive cells in the presence of imatinib
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F21%3A00556532" target="_blank" >RIV/60162694:G44__/21:00556532 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00023736:_____/21:00013170 RIV/68378050:_____/21:00544873 RIV/00216208:11110/21:10431081 RIV/60162694:_____/21:N0000007 RIV/00216208:11310/21:10431081
Výsledek na webu
<a href="https://www.spandidos-publications.com/10.3892/ijo.2020.5163" target="_blank" >https://www.spandidos-publications.com/10.3892/ijo.2020.5163</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3892/ijo.2020.5163" target="_blank" >10.3892/ijo.2020.5163</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Exosomes released by imatinib‑resistant K562 cells contain specific membrane markers, IFITM3, CD146 and CD36 and increase the survival of imatinib‑sensitive cells in the presence of imatinib
Popis výsledku v původním jazyce
Chronic myeloid leukemia (CML) is a malignant hematopoietic disorder distinguished by the presence of a BCR‑ABL1 fused oncogene with constitutive kinase activity. Targeted CML therapy by specific tyrosine kinase inhibitors (TKIs) leads to a marked improvement in the survival of the patients and their quality of life. However, the development of resistance to TKIs remains a critical issue for a subset of patients. The most common cause of resistance are numerous point mutations in the BCR‑ABL1 gene, followed by less common mutations and multiple mutation-independent mechanisms. Recently, exosomes, which are extracellular vesicles excreted from normal and tumor cells, have been associated with drug resistance and cancer progression. The aim of the present study was to characterize the exosomes released by imatinib‑resistant K562 (K562IR) cells. The K562IR‑derived exosomes were internalized by imatinib‑sensitive K562 cells, which thereby increased their survival in the presence of 2 µM imatinib. The exosomal cargo was subsequently analyzed to identify resistance‑associated markers using a deep label‑free quantification proteomic analysis. There were >3,000 exosomal proteins identified of which, 35 were found to be differentially expressed. From this, a total of 3, namely the membrane proteins, interferon‑induced transmembrane protein 3, CD146 and CD36, were markedly upregulated in the exosomes derived from the K562IR cells, and exhibited surface localization. The upregulation of these proteins was verified in the K562IR exosomes, and also in the K562IR cells. Using flow cytometric analysis, it was possible to further demonstrate the potential of CD146 as a cell surface marker associated with imatinib resistance in K562 cells. Taken together, these results suggested that exosomes and their respective candidate surface proteins could be potential diagnostic markers of TKI drug resistance in CML therapy.
Název v anglickém jazyce
Exosomes released by imatinib‑resistant K562 cells contain specific membrane markers, IFITM3, CD146 and CD36 and increase the survival of imatinib‑sensitive cells in the presence of imatinib
Popis výsledku anglicky
Chronic myeloid leukemia (CML) is a malignant hematopoietic disorder distinguished by the presence of a BCR‑ABL1 fused oncogene with constitutive kinase activity. Targeted CML therapy by specific tyrosine kinase inhibitors (TKIs) leads to a marked improvement in the survival of the patients and their quality of life. However, the development of resistance to TKIs remains a critical issue for a subset of patients. The most common cause of resistance are numerous point mutations in the BCR‑ABL1 gene, followed by less common mutations and multiple mutation-independent mechanisms. Recently, exosomes, which are extracellular vesicles excreted from normal and tumor cells, have been associated with drug resistance and cancer progression. The aim of the present study was to characterize the exosomes released by imatinib‑resistant K562 (K562IR) cells. The K562IR‑derived exosomes were internalized by imatinib‑sensitive K562 cells, which thereby increased their survival in the presence of 2 µM imatinib. The exosomal cargo was subsequently analyzed to identify resistance‑associated markers using a deep label‑free quantification proteomic analysis. There were >3,000 exosomal proteins identified of which, 35 were found to be differentially expressed. From this, a total of 3, namely the membrane proteins, interferon‑induced transmembrane protein 3, CD146 and CD36, were markedly upregulated in the exosomes derived from the K562IR cells, and exhibited surface localization. The upregulation of these proteins was verified in the K562IR exosomes, and also in the K562IR cells. Using flow cytometric analysis, it was possible to further demonstrate the potential of CD146 as a cell surface marker associated with imatinib resistance in K562 cells. Taken together, these results suggested that exosomes and their respective candidate surface proteins could be potential diagnostic markers of TKI drug resistance in CML therapy.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30204 - Oncology
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2021
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
International Journal of Oncology
ISSN
1019-6439
e-ISSN
1791-2423
Svazek periodika
58
Číslo periodika v rámci svazku
2
Stát vydavatele periodika
GR - Řecká republika
Počet stran výsledku
13
Strana od-do
238-250
Kód UT WoS článku
000615889800001
EID výsledku v databázi Scopus
2-s2.0-85099317381