Thalidomide downregulates angiogenic genes in bone marrow endothelial cells of patients with active multiple myeloma

Angelo Vacca, Claudio Scavelli, Vittorio Montefusco, Giulia Di Pietro, Antonino Neri, Michela Mattioli, Silvio Bicciato, Beatrice Nico, Domenico Ribatti, Franco Dammacco, Paolo Corradini

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To study the antiangiogenic effect of thalidomide. Patients and Methods: The expression of key angiogenic genes was studied in bone marrow endothelial cells (ECs) of patients with active and nonactive multiple myeloma (MM), monoclonal gammopathies unattributed/unassociated (MG[u]), diffuse large B-cell non-Hodgkin's lymphoma, in a Kaposi's sarcoma (KS) cell line, and in healthy human umbilical vein ECs (HUVECs) following exposure to therapeutic doses of thalidomide. Results: Thalidomide markedly downregulates the genes in a dose-dependent fashion in active MMECs and KS cell line, but upregulates them or is ineffective in nonactive MMECs, MG(u)ECs, NHL-ECs, and in HUVECs. Secretion of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor also diminishes according to the dose in culture conditioned media (CM) of active MMECs and KS, whereas it does not change in the other CM. Conclusion: Inhibition by thalidomide is probably confined to the genes of active MMECs and KS. This would account for its higher efficacy in these diseases.

Original languageEnglish
Pages (from-to)5334-5346
Number of pages13
JournalJournal of Clinical Oncology
Volume23
Issue number23
DOIs
Publication statusPublished - 2005

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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