Expression of the antimicrobial peptide cathelicidin in myeloid cells is required for lung tumor growth
Expression of the antimicrobial peptide cathelicidin in myeloid cells is required for lung tumor growth
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DOI：
10.1038/onc.2013.248
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发表时间：
2014-05-22
期刊：
影响因子：
8
通讯作者：
Bals, R.
中科院分区：
文献类型：
--
作者：
Li, D.;Beisswenger, C.;Bals, R.
抗菌肽，如抗菌肽LL-37/hCAP-18及其小鼠同源抗菌肽（CRAMP）是先天免疫系统的重要效应物，具有直接的抗菌活性。抗菌肽可能参与肿瘤细胞生长的调控。本研究的目的是表征非肿瘤细胞表达的cathelicidin在肿瘤生长的临床前小鼠模型中的作用。野生型和缺乏抽筋的动物暴露于香烟烟雾（CS）中，并注射Lewis肺癌细胞以启动肺部肿瘤的生长。CS暴露显著增加了野生型小鼠肺肿瘤的增殖，但在cramp缺陷小鼠中没有。CS暴露诱导骨髓细胞以camp依赖的方式向肿瘤组织募集。髓系细胞特异性缺乏RelA/p65的小鼠表现出肺中camp阳性细胞募集受损。人细胞的体外研究表明，巨噬细胞中的LL-37/hCAP-18是由来源于癌细胞的可溶性因子诱导的。综上所述，这些数据表明骨髓细胞表达的cathelicidin通过进一步募集炎症细胞促进cs诱导的肺肿瘤生长。对抗菌肽表达的调控涉及髓系p65/RelA和肿瘤细胞可溶性因子。
Antimicrobial peptides, such as the cathelicidin LL-37/hCAP-18 and its mouse homolog cathelicidin-related antimicrobial peptide ( CRAMP), are important effectors of the innate immune system with direct anti-bacterial activity. Cathelicidin is possibly involved in the regulation of tumor cell growth. The aim of this study was to characterize the role of cathelicidin expressed in non-tumorous cells in a preclinical mouse model of tumor growth. Wild-type and CRAMP-deficient animals were exposed to cigarette smoke ( CS) and Lewis lung carcinoma cells were injected to initiate the growth of tumors in the lung. CS exposure significantly increased the proliferation of lung tumors in wild-type mice, but not in CRAMP-deficient mice. CS exposure induced the recruitment of myeloid cell into tumor tissue in a CRAMP-dependent manner. Mice lacking RelA/p65 specifically in myeloid cells showed impaired recruitment of CRAMP-positive cells into the lung. In vitro studies with human cells showed that LL-37/hCAP-18 in macrophages is induced by soluble factors derived from cancer cells. Taken together, these data indicate that cathelicidin expressed from myeloid cells promotes CS-induced lung tumor growth by further recruitment of inflammatory cells. The regulation of cathelicidin expression involves myeloid p65/RelA and soluble factor from tumor cells.