Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development
Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development
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DOI：
10.1038/modpathol.2012.128
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发表时间：
2013-01-01
期刊：
影响因子：
7.5
通讯作者：
Kallioniemi, Anne
中科院分区：
文献类型：
--
作者：
Alarmo, Emma-Leena;Huhtala, Heini;Kallioniemi, Anne
骨形态发生蛋白（BMPs）是细胞外信号分子，属于转化生长因子β (TGF β)超家族，已知可调节细胞增殖、分化和运动，特别是在发育过程中。BMP4在脊椎动物的发育过程中起着不可缺少的作用，而关于BMP4在成体组织中的表达和功能的信息有限。然而，近年来，它对癌症发展和进展的贡献越来越受到关注。功能研究，特别是在乳腺癌中的研究表明，BMP4在抑制细胞增殖和促进细胞迁移和侵袭方面都有作用。为了深入了解BMP4在正常组织和癌症组织中的功能，我们通过免疫组化分析了34种不同正常器官/组织、34种不同肿瘤类型以及486例乳腺癌样本中的BMP4蛋白表达水平，并对BMP4与临床病理参数之间可能存在的关联进行了统计评估。在超过20%的正常和恶性组织中，BMP4高表达。在一些正常上皮细胞，如膀胱和胃，以及鳞状细胞癌中观察到强烈的表达。在乳腺癌中，25%的患者检测到BMP4的强表达，并与低增殖指数和肿瘤复发率增加有关。综上所述，BMP4在正常成人组织的一个亚群中表达，可能有助于组织稳态。然而，在肿瘤中，BMP4的表达水平差异很大，这意味着在不同的肿瘤类型中具有不同的作用。这种作用在乳腺癌中是双期的，因为BMP4的表达与增殖减少和复发增加有关，从而证实了我们之前的体外功能数据。现代病理学杂志（2013）26,10-21；doi: 10.1038 / modpathol.2012.128;2012年8月17日在线发布
Bone morphogenetic proteins (BMPs) are extracellular signaling molecules that belong to the transforming growth factor beta (TGF beta) superfamily and are known to regulate cell proliferation, differentiation and motility, especially during development. BMP4 has an indispensable role in vertebrate development while limited information on BMP4 expression and function exists in adult tissues. Nevertheless, its contribution to cancer development and progression has gained increasing interest in recent years. Functional studies, especially in breast cancer, have implicated BMP4 both in inhibition of cell proliferation and in promotion of cell migration and invasion. To gain an insight into the function of BMP4 in normal and cancer tissues, BMP4 protein expression levels were analyzed by immunohistochemistry in 34 different normal organs/tissues, 34 different tumor types and finally in 486 breast cancer samples where possible associations between BMP4 and clinicopathological parameters were statistically evaluated. In over 20% of normal and malignant tissues, BMP4 was expressed at high level. Strong expression was observed particularly in some normal epithelial cells, such as bladder and stomach, and in squamous cell carcinomas. In breast cancer, strong BMP4 expression was detected in 25% of patients, and was associated with low proliferation index and increased frequency of tumor recurrence. Taken together, BMP4 is expressed in a subset of normal adult tissues and is likely to contribute to tissue homeostasis. However, in tumors, BMP4 expression levels vary considerably, implying diverse roles in different tumor types. This role is biphasic in breast cancer as BMP4 expression is linked to reduced proliferation and increased recurrence, thus corroborating our previous in-vitro functional data. Modern Pathology (2013) 26, 10-21; doi:10.1038/modpathol.2012.128; published online 17 August 2012