Expression of the antimicrobial peptide cathelicidin in myeloid cells is required for lung tumor growth

被引:41
作者
Li, D. [1 ]
Beisswenger, C. [1 ]
Herr, C. [1 ]
Schmid, R. M. [2 ]
Gallo, R. L. [3 ]
Han, G. [1 ]
Zakharkina, T. [1 ]
Bals, R. [1 ]
机构
[1] Saarland Univ Hosp, Dept Internal Med 5, D-66421 Homburg, Germany
[2] Tech Univ Munich, Dept Internal Med 2, D-80290 Munich, Germany
[3] Univ Calif San Diego, Div Dermatol, San Diego, CA 92103 USA
关键词
lung cancer; cathelicidin; antimicrobial peptide; inflammation; macrophage; HOST-DEFENSE; PROTEIN HCAP18/LL-37; HUMAN KERATINOCYTES; LL-37; CANCER; GENE; RECEPTOR; MURINE; SKIN; PROLIFERATION;
D O I
10.1038/onc.2013.248
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2709 / 2716
页数:8
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