thymosin-beta(4) and Multiple-Myeloma

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.

Topics: Animals; Apoptosis; Bone Marrow; Humans; Mice; Multiple Myeloma; Thymosin

Thymosin beta4 (Tbeta4) is a polypeptide involved in cellular proliferation, differentiation, and migration, over-expressed in several tumor entities. We evaluated its expression and function in 298 newly diagnosed multiple myeloma patients and the murine 5TMM model. Mean Tbeta4 expression was significantly lower in myeloma cells compared to normal plasma cells (P<0.001). The same observation can be made in the 5TMM-mouse model by qRT-PCR and ELISA. Here, Tbeta4 overexpression by lentiviral transduction of 5T33MMvt-cells led to significantly decreased proliferative and migratory capacities and increased sensitivity to apoptosis-induction. Mice injected with Tbeta4 over-expressing myeloma cells showed a longer survival compared to mice injected with controls (88,9 vs. 65,9 days, P<0.05). In 209 MM patients treated with high-dose therapy and autologous stem cell transplantation, expression of Tbeta4 below the median was associated with a significantly shorter event free survival (37.6 vs. 26.2 months, P<0.05). In conclusion, our results indicate a possible tumor suppressive function of Tbeta4.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Disease Models, Animal; Down-Regulation; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Mice; Mice, Inbred C57BL; Multiple Myeloma; Prognosis; Survival Rate; Thymosin; Tumor Suppressor Proteins