αvβ3 Integrin expression and mitogenic effects by thyroid hormones in chronic lymphocytic leukemia

Uri Abadi, Avivit Weisz, Dvora Kidron, Aviva Katzav, Aleck Hercbergs, Paul J. Davis, Martin H. Ellis, Osnat Ashur-Fabian*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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. Meth-ods: 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 immunohisto-chemistry (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.

Original languageEnglish
Article number1766
JournalJournal of Clinical Medicine
Volume10
Issue number8
DOIs
StatePublished - 2 Apr 2021

Keywords

  • Chronic lymphocytic leukemia
  • Thyroid hormone
  • αvβ3 integrin

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