Expression of angiogenic factors including VEGFs and the effects of hypoxia and thalidomide on human myeloma cells.
Angiogenic factors are major causes of tumor progression in hematological malignancies, particularly multiple myeloma, as well as solid tumors. The introduction of thalidomide as an anti-angiogenic agent in myeloma treatment has demonstrated the importance of angiogenic factors in the progression of myeloma. However, the direct effects of angiogenic factors, particularly VEGFs, hypoxia, and thalidomide, on myeloma cells are not been documented. In this study, we demonstrate increased expression and production levels of VEGF in myeloma compared to non-myelomatous hematological lines, resistance to hypoxia and enhancement of VEGF-A production by hypoxia in myeloma, and direct growth inhibition of myeloma cells due to apoptosis and G1 arrest caused by TNFalpha upregulation induced by thalidomide. These findings may encourage the clinical use of anti-angiogenic agents for their cytostatic effects and the prevention of progression.
Yata
Kenichiro
K
Department of Internal Medicine, Division of Hematology, Kawasaki Medical School, Okayama 701-0192, Japan.
Otsuki
Takemi
T
Kurebayashi
Junichi
J
Uno
Masako
M
Fujii
Tomohiro
T
Yawata
Yoshihito
Y
Takata
Akiko
A
Hyodoh
Fuminori
F
Sugihara
Takashi
T
D043925:Angiogenesis Inducing Agents / Q000096:biosynthesis* / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D015687:Cell Hypoxia; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013792:Thalidomide / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A
D043925:Angiogenesis Inducing Agents; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide