Antimyeloma effects of a novel synthetic retinoid Am80 (Tamibarotene) through inhibition of angiogenesis

T. Sanda, T. Kuwano, shintaro nakao, S. Iida, T. Ishida, H. Komatsu, K. Shudo, M. Kuwano, M. Ono, R. Ueda

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

In multiple myeloma (MM), the interaction between myeloma cells and bone marrow microenvironment has an important role in the pathogenesis of MM. We first examined the inducing effect of myeloma cells on migration of human umbilical vein vascular endothelial cells (HUVECs). Five myeloma cell lines produced varying amounts of VEGF, and migration of HUVECs was induced by coculture with myeloma cells. We next examined the inhibitory effect of a novel synthetic retinoid Am80 (Tamibarotene) on both myeloma cells and HUVECs. Am80 is specific for the retinoic-acid receptor-α/β, and has therapeutic effects in all-trans retinoic acid resistant acute promyelocytic leukemia. Am80 slightly inhibited the growth of both myeloma cells and HUVECs, and remarkably inhibited the growth of HUVECs stimulated by VEGF. Am80 showed little growth inhibition of bone marrow stromal cells (BMSCs), but it markedly inhibited migration of HUVECs by cocultured myeloma cells. Am80 inhibited VEGF-induced phosphorylation of VEGF receptor. In addition, VEGF-induced formation of tube-like structures in vitro and neovascularization in mouse corneas were significantly inhibited by Am80. These findings clearly demonstrate that Am80 is a potential inhibitor of angiogenesis caused by the interaction between vascular endothelial cells and myeloma cells, and might be a useful therapeutic agent against MM.

Original languageEnglish
Pages (from-to)901-909
Number of pages9
JournalLeukemia
Volume19
Issue number6
DOIs
Publication statusPublished - Jan 1 2005

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Retinoids
Human Umbilical Vein Endothelial Cells
Endothelial Cells
Vascular Endothelial Growth Factor A
Multiple Myeloma
Growth
Acute Promyelocytic Leukemia
Retinoic Acid Receptors
Vascular Endothelial Growth Factor Receptor
Angiogenesis Inhibitors
tamibarotene
Therapeutic Uses
Coculture Techniques
Tretinoin
Mesenchymal Stromal Cells
Bone Marrow Cells
Cornea
Cell Movement
Phosphorylation
Cell Line

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Antimyeloma effects of a novel synthetic retinoid Am80 (Tamibarotene) through inhibition of angiogenesis. / Sanda, T.; Kuwano, T.; nakao, shintaro; Iida, S.; Ishida, T.; Komatsu, H.; Shudo, K.; Kuwano, M.; Ono, M.; Ueda, R.

In: Leukemia, Vol. 19, No. 6, 01.01.2005, p. 901-909.

Research output: Contribution to journalArticle

Sanda, T, Kuwano, T, nakao, S, Iida, S, Ishida, T, Komatsu, H, Shudo, K, Kuwano, M, Ono, M & Ueda, R 2005, 'Antimyeloma effects of a novel synthetic retinoid Am80 (Tamibarotene) through inhibition of angiogenesis', Leukemia, vol. 19, no. 6, pp. 901-909. https://doi.org/10.1038/sj.leu.2403754
Sanda, T. ; Kuwano, T. ; nakao, shintaro ; Iida, S. ; Ishida, T. ; Komatsu, H. ; Shudo, K. ; Kuwano, M. ; Ono, M. ; Ueda, R. / Antimyeloma effects of a novel synthetic retinoid Am80 (Tamibarotene) through inhibition of angiogenesis. In: Leukemia. 2005 ; Vol. 19, No. 6. pp. 901-909.
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