Expression, regulation and clinical significance of bone morphogenetic protein 6 in esophageal squamous‐cell carcinoma
Expression, regulation and clinical significance of bone morphogenetic protein 6 in esophageal squamous‐cell carcinoma
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DOI：
10.1002/(sici)1097-0215(19990924)83:1
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发表时间：
1999-09
影响因子：
6.4
通讯作者：
M. Raida;M. Sarbia;J. Clement;S. Adam;H. Gabbert;K. Höffken
中科院分区：
文献类型：
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作者：
M. Raida;M. Sarbia;J. Clement;S. Adam;H. Gabbert;K. Höffken
骨形态发生蛋白（BMP）是一种多功能的细胞因子。BMP-6参与角质形成的早期步骤。食管鳞状细胞癌常表现为异常角化。本研究的目的是检测BMP-6在食管癌中的表达和调节，并确定其表达与肿瘤特征和生存的关系。使用石蜡包埋的肿瘤标本进行抗生物素蛋白-生物素-过氧化物酶染色，这些标本采集自172例接受了潜在治愈性手术的食管鳞状细胞癌患者。采用特异性RT-PCR检测食管鳞状细胞癌细胞系科洛-680 N和下咽鳞状细胞癌细胞系FaDu中BMP-6和EGF-受体的表达。在标准细胞培养条件下，科洛-680 N和FaDu细胞显示出不同的BMP-6表达，而在无血清条件下，几乎检测不到BMP-6表达。加入EGF或EGF相关生长因子可增加BMP-6 mRNA的含量。免疫组织化学显示，所有172例肿瘤均表现出BMP-6的胞浆免疫反应性。BMP-6蛋白含量与肿瘤分化程度呈负相关（p < 0.01）。单因素生存分析显示，74例低免疫反应性肿瘤患者的2年和5年生存率（50.0%/27.7%）高于75例高免疫反应性肿瘤患者（33.3%/21.6%）。（p < 0.05）。我们得出结论，BMP-6在食管鳞状细胞癌中表达。EGF受体的激活对于调节BMP-6的表达至关重要。BMP-6蛋白含量与肿瘤细胞分化程度相关，可能增加预后不良的指征。Int. J. Cancer 83：38-44，1999.© 1999 Wiley利斯公司
Bone morphogenetic proteins (BMPs) are multifunctional cytokines. BMP‐6 is involved in early steps of keratinogenesis. Esophageal squamous‐cell carcinoma often shows abnormal keratinization. The aim of this study was to examine the expression and regulation of BMP‐6 in esophageal carcinoma and to determine the relationship of its expression with tumor characteristics and survival. Avidin‐biotin‐peroxidase staining was performed using paraffin‐wax‐embedded tumor specimens collected from 172 patients with esophageal squamous‐cell carcinoma, who underwent potentially curative surgery. Expression of BMP‐6 and EGF‐receptor in the esophageal‐squamous‐cell‐carcinoma cell line COLO‐680N and the hypopharyngeal‐squamous‐cell‐carcinoma cell line FaDu was assayed with specific RT‐PCR. In standard cell‐cultivation conditions, COLO‐680N and FaDu cells showed distinct expression of BMP‐6, whereas in serum‐free conditions BMP‐6 expression was hardly detectable. The addition of EGF or EGF‐related growth factors could elevate BMP‐6 mRNA content. Immunohistochemically, all 172 tumors exhibited cytoplasmic immunoreactivity for BMP‐6. The content of BMP‐6 protein was inversely correlated with tumor differentiation (p < 0.01). Univariate survival analysis revealed that 74 patients with tumors of low immunoreactivity had higher 2‐year and 5‐year survival rates (50.0%/27.7%) than 75 patients with tumors of high immunoreactive scores (33.3%/21.6%). (p < 0.05). We conclude that BMP‐6 is expressed in esophageal squamous‐cell carcinoma. EGF‐receptor activation is crucial for regulation of BMP‐6 expression. BMP‐6 protein content is correlated with the grade of tumor‐cell differentiation and may add to indications of poor prognosis. Int. J. Cancer 83:38–44, 1999. © 1999 Wiley‐Liss, Inc.