Department of Hematology, CHU University of Liège, Liège, Belgium.
Ann N Y Acad Sci. 2010 Apr;1194:125-9. doi: 10.1111/j.1749-6632.2010.05470.x.
Multiple myeloma (MM) is a malignancy characterized by the accumulation of monoclonal plasma cells in the bone marrow (BM). Because of the known involvement of thymosin beta4 (Tbeta4) in metastasis of tumor cells, we examined the expression and role of Tbeta4 in MM disease. In a large patient population, we demonstrated that Tbeta4 expression was significantly lower in myeloma cells compared to normal plasma cells and that patients with a high Tbeta4 expression had a longer event free and overall survival. The decreased Tbeta4 expression was also found in the murine 5TMM model. To study its function, we overexpressed the Tbeta4 gene in 5T33MMvt cells by lentiviral transduction. These cells demonstrated a decreased proliferative capability and an increased sensitivity to apoptosis. Mice injected with Tbeta4-overexpressing cells showed a prolonged survival compared to mice injected with controls. In contrast to its role in solid tumors, we found a decreased expression in myeloma cells compared to their normal counterpart and studies with overexpression of the Tbeta4 gene indicated a tumor suppressive function of Tbeta4 in myeloma development.
多发性骨髓瘤（MM）是一种恶性肿瘤，其特征是骨髓（BM）中单克隆浆细胞的积累。由于胸腺素 beta4（Tbeta4）已知参与肿瘤细胞的转移，我们研究了 Tbeta4 在 MM 疾病中的表达和作用。在大量患者人群中，我们证明与正常浆细胞相比，骨髓瘤细胞中的 Tbeta4 表达明显降低，并且 Tbeta4 表达较高的患者无事件生存期和总生存期更长。在 5TMM 小鼠模型中也发现了 Tbeta4 表达的降低。为了研究其功能，我们通过慢病毒转导在 5T33MMvt 细胞中过表达 Tbeta4 基因。这些细胞表现出增殖能力降低和凋亡敏感性增加。与对照组相比，注射 Tbeta4 过表达细胞的小鼠的存活时间延长。与在实体瘤中的作用相反，我们发现与正常细胞相比，骨髓瘤细胞中的表达降低，并且过表达 Tbeta4 基因的研究表明 Tbeta4 在骨髓瘤发展中具有肿瘤抑制功能。
