Yata Kenichiro, Otsuki Takemi, Kurebayashi Junichi, Uno Masako, Fujii Tomohiro, Yawata Yoshihito, Takata Akiko, Hyodoh Fuminori, Sugihara Takashi
Department of Internal Medicine, Division of Hematology, Kawasaki Medical School, Okayama 701-0192, Japan.
Int J Oncol. 2003 Jan;22(1):165-73.
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.
血管生成因子是血液系统恶性肿瘤尤其是多发性骨髓瘤以及实体瘤中肿瘤进展的主要原因。沙利度胺作为一种抗血管生成药物被引入骨髓瘤治疗，这已证明血管生成因子在骨髓瘤进展中的重要性。然而，血管生成因子，特别是血管内皮生长因子（VEGF）、缺氧和沙利度胺对骨髓瘤细胞的直接作用尚未见报道。在本研究中，我们证明与非骨髓瘤血液系相比，骨髓瘤中VEGF的表达和产生水平增加，骨髓瘤对缺氧具有抗性且缺氧可增强VEGF-A的产生，以及沙利度胺诱导的肿瘤坏死因子α（TNFα）上调导致凋亡和G1期阻滞，从而对骨髓瘤细胞产生直接生长抑制作用。这些发现可能会促使抗血管生成药物因其细胞抑制作用和预防疾病进展而在临床上得到应用。
