Thymosin β4 has tumor suppressive effects and its decreased expression results in poor prognosis and decreased survival in multiple myeloma.
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.
Caers
Jo
J
Laboratory of Hematology and Immunology, Vrije Universiteit Brussel, Myeloma Center Brussels, Brussels, Belgium.
Hose
Dirk
D
Kuipers
Ine
I
Bos
Tomas Jan
TJ
Van Valckenborgh
Els
E
Menu
Eline
E
De Bruyne
Elke
E
Goldschmidt
Hartmut
H
Van Camp
Ben
B
Klein
Bernard
B
Vanderkerken
Karin
K
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate / Q000639:trends; D013947:Thymosin / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D000099201:Thymosin beta(4)
D013947:Thymosin; D025521:Tumor Suppressor Proteins; D000099201:Thymosin beta(4)