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

Result code in 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>

Alternative codes found

RIV/00023736:_____/21:00013170 RIV/68378050:_____/21:00544873 RIV/00216208:11110/21:10431081 RIV/60162694:_____/21:N0000007 RIV/00216208:11310/21:10431081

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

—

Type

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

CEP classification

—

OECD FORD branch

30204 - Oncology

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

International Journal of Oncology

ISSN

1019-6439

e-ISSN

1791-2423

Volume of the periodical

58

Issue of the periodical within the volume

2

Country of publishing house

GR - GREECE

Number of pages

13

Pages from-to

238-250

UT code for WoS article

000615889800001

EID of the result in the Scopus database

2-s2.0-85099317381