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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
来源:
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.
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页码:2709 / 2716
页数:8
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