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αvβ3 Integrin Expression and Mitogenic Effects by Thyroid Hormones in Chronic Lymphocytic Leukemia

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. The thyroid hormones, T3 and T4, bind the αvβ3 integrin and activate phosphorylates ERK (pERK). These tumor-promoting actions were reported in a number of malignancies, but not in CLL. Methods: Primary cells from 22 CL...

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Autores principales: Abadi, Uri, Weisz, Avivit, Kidron, Dvora, Katzav, Aviva, Hercbergs, Aleck, Davis, Paul J., Ellis, Martin H., Ashur-Fabian, Osnat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073405/
https://www.ncbi.nlm.nih.gov/pubmed/33921634
http://dx.doi.org/10.3390/jcm10081766
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author Abadi, Uri
Weisz, Avivit
Kidron, Dvora
Katzav, Aviva
Hercbergs, Aleck
Davis, Paul J.
Ellis, Martin H.
Ashur-Fabian, Osnat
author_facet Abadi, Uri
Weisz, Avivit
Kidron, Dvora
Katzav, Aviva
Hercbergs, Aleck
Davis, Paul J.
Ellis, Martin H.
Ashur-Fabian, Osnat
author_sort Abadi, Uri
collection PubMed
description Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. The thyroid hormones, T3 and T4, bind the αvβ3 integrin and activate phosphorylates ERK (pERK). These tumor-promoting actions were reported in a number of malignancies, but not in CLL. Methods: Primary cells from 22 CLL patients were verified for disease markers (CD5/CD19/CD23) and analyzed for αvβ3 by flow cytometry (FC), ImageStream, Western blots (WB), and immunohistochemistry (IHC) in archival bone marrow (BM, n = 6) and lymph node (LN, n = 5) tissues. Selected samples (n = 8) were incubated with T3 (1–100 nM) or T4 (0.1–10 µM) for 30 min, and the expression levels of αvβ3, pERK and PCNA (cell proliferation marker) were determined (WB). Results: αvβ3 was detected on the membrane of circulating CLL cells and in the BM but not in the LN. T3 and T4 enhanced αvβ3 protein levels in primary CLL cells. Similarly, pERK and PCNA were rapidly induced in response to T3 and T4 exposure. Conclusions: αvβ3 integrin is expressed on primary CLL cells and is induced by thyroid hormones. We further suggest that the hormones are mitogenic in these cells, presumably via αvβ3-mediated signaling.
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spelling pubmed-80734052021-04-27 αvβ3 Integrin Expression and Mitogenic Effects by Thyroid Hormones in Chronic Lymphocytic Leukemia Abadi, Uri Weisz, Avivit Kidron, Dvora Katzav, Aviva Hercbergs, Aleck Davis, Paul J. Ellis, Martin H. Ashur-Fabian, Osnat J Clin Med Article Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. The thyroid hormones, T3 and T4, bind the αvβ3 integrin and activate phosphorylates ERK (pERK). These tumor-promoting actions were reported in a number of malignancies, but not in CLL. Methods: Primary cells from 22 CLL patients were verified for disease markers (CD5/CD19/CD23) and analyzed for αvβ3 by flow cytometry (FC), ImageStream, Western blots (WB), and immunohistochemistry (IHC) in archival bone marrow (BM, n = 6) and lymph node (LN, n = 5) tissues. Selected samples (n = 8) were incubated with T3 (1–100 nM) or T4 (0.1–10 µM) for 30 min, and the expression levels of αvβ3, pERK and PCNA (cell proliferation marker) were determined (WB). Results: αvβ3 was detected on the membrane of circulating CLL cells and in the BM but not in the LN. T3 and T4 enhanced αvβ3 protein levels in primary CLL cells. Similarly, pERK and PCNA were rapidly induced in response to T3 and T4 exposure. Conclusions: αvβ3 integrin is expressed on primary CLL cells and is induced by thyroid hormones. We further suggest that the hormones are mitogenic in these cells, presumably via αvβ3-mediated signaling. MDPI 2021-04-19 /pmc/articles/PMC8073405/ /pubmed/33921634 http://dx.doi.org/10.3390/jcm10081766 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Abadi, Uri
Weisz, Avivit
Kidron, Dvora
Katzav, Aviva
Hercbergs, Aleck
Davis, Paul J.
Ellis, Martin H.
Ashur-Fabian, Osnat
αvβ3 Integrin Expression and Mitogenic Effects by Thyroid Hormones in Chronic Lymphocytic Leukemia
title αvβ3 Integrin Expression and Mitogenic Effects by Thyroid Hormones in Chronic Lymphocytic Leukemia
title_full αvβ3 Integrin Expression and Mitogenic Effects by Thyroid Hormones in Chronic Lymphocytic Leukemia
title_fullStr αvβ3 Integrin Expression and Mitogenic Effects by Thyroid Hormones in Chronic Lymphocytic Leukemia
title_full_unstemmed αvβ3 Integrin Expression and Mitogenic Effects by Thyroid Hormones in Chronic Lymphocytic Leukemia
title_short αvβ3 Integrin Expression and Mitogenic Effects by Thyroid Hormones in Chronic Lymphocytic Leukemia
title_sort αvβ3 integrin expression and mitogenic effects by thyroid hormones in chronic lymphocytic leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073405/
https://www.ncbi.nlm.nih.gov/pubmed/33921634
http://dx.doi.org/10.3390/jcm10081766
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