The host defence peptide LL-37/hCAP-18 is a growth factor for lung cancer cells
The host defence peptide LL-37/hCAP-18 is a growth factor for lung cancer cells
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DOI：
10.1016/j.lungcan.2007.07.014
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发表时间：
2008-01-01
期刊：
影响因子：
5.3
通讯作者：
Bals, Robert
中科院分区：
文献类型：
--
作者：
von Haussen, Judith;Koczulla, Rembert;Bals, Robert
癌症的发展可以看作是修复失调。抗菌肽（AMPs）是先天免疫系统的效应分子，具有直接的抗菌活性。除了这种宿主防御功能外，几种amp还在炎症和组织修复的调节中发挥作用。本研究旨在探讨人抗菌肽AMP LL-37/hCAP-18是否参与肺癌的生物学过程。研究发现，人肿瘤细胞系不同程度地表达人抗菌肽LL-37/hCAP-18 mRNA和肽。人肺癌的免疫组化结果显示，该肽主要在腺癌和鳞癌中表达。5 ng/ml外源LL-37对肿瘤细胞株的增殖和生长有促进作用。在分子水平上，LL-37诱导表皮生长因子受体（EGFR）的磷酸化和下游MAP激酶信号通路的激活。通过强力霉素调控的启动子系统稳定过表达该肽的肺癌细胞也表现出更快的生长。当这些细胞被皮下注射到裸鼠体内时，cathelicidin的过表达导致致瘤性增加，肿瘤的形成明显变大。总之，cathelicidin在人肺癌中表达。在体外和动物模型中，这种肽激活肿瘤细胞，导致细胞生长增加。宿主防御肽cathelicidin LL-37/hCAP-18是人肺癌的生长因子。2007爱思唯尔爱尔兰有限公司版权所有。
Cancer development can be viewed as dysregulated repair. Antimicrobial peptides (AMPs) are effector molecules of the innate immune system with direct antimicrobial activity. Beside this host defence function several AMPs play a role in the regulation of inflammation and tissue repair. The aim of the present study was to investigate whether the human cathelicidin AMP LL-37/hCAP-18 is involved in the biology of Lung cancer.Human cancer cell lines were found to express the human cathelicidin LL-37/hCAP-18 mRNA and peptide at different levels. Immunohistochemistry of human lung cancers showed that the peptide is expressed mostly in adenocarcinoma and squamous cell carcinoma. Application of exogenous LL-37 at Low concentrations of 5 ng/ml to cancer cell lines increased proliferation and growth of anchorage-independent colonies. At the molecular level, LL-37 induced phosphorylation of the epidermal growth factor receptor (EGFR) and activation of downstream MAP kinase signalling pathways. Lung cancer cell tines that stably overexpress the peptide by means of a doxycycline-regulated promoter system also showed a faster growth. When these cell tines were injected subcutaneously into nude mice, cathelicidin overexpression resulted in increased tumourigenicity and the formation of significantly larger tumours.In conclusion, cathelicidin is expressed in human lung cancers. The peptide activates tumour cells resulting in increased cell growth in vitro and in an animal model. The host defence peptide cathelicidin LL-37/hCAP-18 acts as growth factor for human lung cancer. (c) 2007 Elsevier Ireland Ltd. All rights reserved.