Ke Z, Zhang X, Ma L, Wang L
Department of Pathology, Medical School of Sun Yat-sen University, Guangzhou, Province, Guandong, China.
Neoplasma. 2008;55(4):323-9.
The DPC4 influences tumourigenesis and tumor progression by various mechanisms, including angiogenesis. The aim of this study was to determine whether the expression of DPC4 is related to the angiogenesis in lung cancer and whether it could be involved in its clinical behaviour. Immunohistochemistry revealed that DPC4 was expressed at high level in normal broncho-tracheal epithelium, but at low level in tumor tissues, and closely correlated with tumor lymph node metastasis. This result was further confirmed by Western blot analysis. Furthermore, carcinomas with high DPC4 expression demonstrated low VEGF expression and low MVD (microvessel density) labelled with CD34. In addition, DPC4 siRNA in A549 cells also showed that DPC4 could decrease VEGF protein and mRNA expression, and increase TSP1 protein and mRNA expression. Our findings indicated that DPC4 might be an important biomarker for malignant transformation and be involved in preventing the tumor metastasis by inhibiting tumor angiogenesis.
DPC4 通过多种机制影响肿瘤发生和肿瘤进展，包括血管生成。本研究的目的是确定 DPC4 的表达是否与肺癌中的血管生成相关，以及它是否可能参与其临床行为。免疫组织化学显示，DPC4 在正常支气管上皮中高表达，但在肿瘤组织中低表达，且与肿瘤淋巴结转移密切相关。蛋白质印迹分析进一步证实了这一结果。此外，DPC4 高表达的癌组织显示 VEGF 表达低，且 CD34 标记的微血管密度（MVD）低。此外，A549 细胞中的 DPC4 小干扰 RNA 也表明，DPC4 可降低 VEGF 蛋白和 mRNA 表达，并增加 TSP1 蛋白和 mRNA 表达。我们的研究结果表明，DPC4 可能是恶性转化的重要生物标志物，并通过抑制肿瘤血管生成参与预防肿瘤转移。
