title: Thyroid hormone regulates adhesion, migration and matrix metalloproteinase 9 activity via αvβ3 integrin in myeloma cells.
abstract: Thyroid hormone (3,5,3'-triiodothyronine, T3; L-thyroxine, T4) enhances cancer cell proliferation, invasion and angiogenesis via a discrete receptor located near the RGD recognition site on αvβ3 integrin. Tetraiodothyroacetic acid (tetrac) and its nanoparticulate formulation interfere with binding of T3/T4 to the integrin. This integrin is overexpressed in multiple myeloma (MM) and other cancers. MM cells interact with αvβ3 integrin to support growth and invasion. Matrix metalloproteinases (MMPs) are a family of enzymes active in tissue remodeling and cancer. The association between integrins and MMPs secretion and action is well established. In the current study, we examined the effects of thyroid hormone on myeloma cell adhesion, migration and MMP activity. We show that T3 and T4 increased myeloma adhesion to fibronectin and induced αvβ3 clustering. In addition, the hormones induced MMP-9 expression and activation via αvβ3 and MAPK induction. Bortezomib, a standard myeloma treatment, caused a decrease in activity/quantity of MMPs and thyroid hormone opposed this effect. RGD peptide and tetrac impaired the production of MMP-9 in cell lines and in primary BM cells from myeloma patients. In conclusion, thyroid hormone-dependent regulation via αvβ3 of myeloma cell adhesion and MMP-9 production may play a role in myeloma migration and progression.
authors: Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel; Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Keren
authors: K
authors: Cohen
authors: Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Nir
authors: N
authors: Flint
authors: Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Shachar
authors: S
authors: Shalev
authors: Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Daniel
authors: D
authors: Erez
authors: Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Tal
authors: T
authors: Baharal
authors: Department of Medicine, Albany Medical College, Albany, NY, USA.
authors: Paul J
authors: PJ
authors: Davis
authors: Radiation Oncology, Cleveland Clinic, Cleveland, OH, USA.
authors: Aleck
authors: A
authors: Hercbergs
authors: Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Martin
authors: M
authors: Ellis
authors: Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel; Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Osnat
authors: O
authors: Ashur-Fabian
mesh_terms: D000069286:Bortezomib / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009101:Multiple Myeloma / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013974:Thyroxine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D014284:Triiodothyronine; D000069286:Bortezomib; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C011126:tetraiodothyroacetic acid; D013974:Thyroxine