کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3446681 | 1595497 | 2011 | 10 صفحه PDF | دانلود رایگان |
Background and AimsBone morphogenetic proteins (BMPs) have recently been shown to be involved in the genesis and progression of a wide variety of carcinomas. The present study was undertaken to estimate the effect of BMP-4 on squamous cell carcinoma of the head and neck (SCCHN) in tissue and cell levels.MethodsIn this study, immunohistochemistry, Western blotting and RT-PCR were utilized to detect the expression of BMP-4, Smad1 and phosphorylated Smad1 in SCCHN tissues or SCCHN cell lines. Those three proteins in tissues were further correlated with prognosis of SCCHN by Kaplan-Meier analysis. The epithelial-mesenchymal transition (EMT)-associated changes in SCCHN cells were detected after stimulation by human BMP-4 recombinant protein and knockdown of Smad1 gene. Meanwhile, the effect on invasiveness and migration was evaluated by invasion and scratch assays, respectively.ResultsBMP-4 and p-Smad1 protein were overexpressed in SCCHN tissues with cervical lymph node metastasis, which was significantly higher than those without metastasis. The expression of BMP-4 and p-Smad1 protein was negatively correlated with the prognosis of SCCHN. BMP-4 promoted the invasiveness and migration through EMT, which was demonstrated by morphological alterations, loss of E-cadherin, increase of vimentin and activation of the Smad1 signal pathway. Knockdown of Smad1 expression suppressed BMP-4 induced EMT in both cell lines and weakened the invasiveness and migration of Tu686 and Tu212 in vitro.ConclusionsOur results demonstrate that BMP-4 protein may contribute to the malignant metastasis of SCCHN, which presents as a novel prognostic marker and a potential therapeutic target for patients with SCCHN.
Journal: Archives of Medical Research - Volume 42, Issue 2, February 2011, Pages 128–137