Role of thymosin beta4 in XXXX @entity3 and angiogenesis.

@entity5 @entity19 @entity2 @entity3 @entity320
BACKGROUND: Expression of the small peptide thymosin beta4 is associated with angiogenesis induction, accelerated wound healing, and the metastatic potential of @entity5 cells. However, little is known about the mechanism(s) by which thymosin beta4 promotes @entity3 . METHODS: Northern blot analysis and immunohistochemistry were used to examine thymosin beta4 expression in @entity19 @entity320 B16 cell lines and in @entity19 cells derived from metastatic @entity19 @entity2 , respectively. @entity19 cells infected with adenoviruses containing a thymosin beta4 expression vector or an empty vector were injected subcutaneously and intravenously into C57BL/6 @entity19 to evaluate @entity5 growth and metastatic potential, respectively. In vitro assays were used to study cell migration, invasion, matrix metalloproteinase activity, cell proliferation, and angiogenic activity of adenovirus-infected @entity19 cells. Statistical significance of all results was analyzed by two-tailed Student's t tests. RESULTS: Thymosin beta4 mRNA was expressed in primary cultured @entity19 cells derived from lung metastases and in @entity19 cells that had formed @entity2 after being injected into @entity19 but not in the B16-F1, @entity19 , or B16-BL6 cell lines. The mean @entity5 sizes in @entity19 20 days after injection with @entity19 cells infected with thymosin beta4-expressing adenovirus and with control adenovirus were 21.7 mm (95% confidence interval [CI] = 17.7 to 25.7 mm) and 13.3 mm (95% CI = 11.1 to 15.3 mm), respectively (difference = 8.4 mm; P =.036). The mean numbers of metastatic lung nodules in @entity19 (n = 20) 2 weeks after intravenous injection with thymosin beta4-expressing adenovirus and with control adenovirus were 46.7 (95% CI = 35.0 to 57.7) and 10.9 (95% CI = 6.2 to 15.6), respectively (difference = 35.8 metastatic lung nodules, P<.001). Thymosin beta4 overexpression was associated with a mean 2.3-fold increase (95% CI = 1.9- to 2.7-fold increase; P<.001) in @entity19 cell migration and a mean 4.4-fold increase (95% CI = 3.3- to 5.5-fold increase; P<.001) in the number of blood vessels in solid @entity5 derived from injected @entity19 cells but had no effect on cell invasion, proliferation, or matrix metalloproteinase activity. This induction of angiogenesis by thymosin beta4 was associated with induction of vascular endothelial growth factor expression. CONCLUSION: Thymosin beta4 may stimulate @entity5 @entity3 by activating cell migration and angiogenesis.
