Relevance of the thyroid hormones-αvβ3 pathway in primary myeloma bone marrow cells and to bortezomib action

Keren Cohen, Martin Ellis, Elena Shinderman, Shafik Khoury, Paul J. Davis, Aleck Hercbergs, Osnat Ashur-Fabian

Research output: Contribution to journalArticlepeer-review

Abstract

Abstract Thyroid hormones (T3 and T4) induce proliferation in multiple myeloma (MM) cell lines via the αvβ3 integrin-mitogen-activated protein kinase (MAPK) pathway. We further show in primary MM bone marrow (BM) samples (n = 9) induction of cell viability by 1 nM T3 (13%, p < 0.002) and more potently by 100 nM T4 (21-45%, p < 0.0002) and a quick (1 h) and long-lasting (24 h) pERK activation, which was inhibited in the presence of β3 but not β1 blocking antibodies. Involvement of the integrin was further shown by two disintegrins, Arg-Gly-Asp (RGD) and echistatin peptides, which occluded the effects of T3/T4 on viability, proliferating cell nuclear antigen (PCNA) (proliferation marker) and apoptotic gene expression. Lastly, T3/T4 significantly opposed bortezomib (25 nM) cytotoxicy, as confirmed by several methods. In summary, our results imply that endogenous thyroid hormones in myeloma are factors that may support cell growth, with relevance to bortezomib action.

Original languageEnglish
Pages (from-to)1107-1114
Number of pages8
JournalLeukemia and Lymphoma
Volume56
Issue number4
DOIs
StatePublished - 1 Apr 2015

Keywords

  • Integrin
  • Myeloma
  • Thyroid hormone
  • αvβ3

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