Expression of the antimicrobial peptide cathelicidin in myeloid cells is required for lung tumor growth
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Published on: June 16, 2018
D Li1, C Beisswenger1, C Herr1
1Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
Abstract:
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.
Insights
Cigarette smoke promotes lung tumor growth by increasing cathelicidin, an antimicrobial peptide. This peptide, produced by myeloid cells, recruits more inflammatory cells, fueling tumor expansion.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Antimicrobial peptides, including cathelicidins like LL-37/hCAP-18 and CRAMP, are key components of the innate immune system.
- Cathelicidins have been implicated in regulating tumor cell growth, but their specific role in non-tumorous cells during tumor progression is not fully understood.
Purpose of the Study:
- To investigate the role of cathelicidin expressed in non-tumorous cells in a preclinical mouse model of lung tumor growth.
- To elucidate the mechanisms underlying cathelicidin's involvement in cigarette smoke-induced tumor progression.
Main Methods:
- Utilized wild-type and CRAMP-deficient mice exposed to cigarette smoke (CS) and Lewis lung carcinoma cells.
- Analyzed the recruitment of myeloid cells into tumor tissue.
- Investigated the role of myeloid p65/RelA in cathelicidin expression.
- Conducted in vitro studies using human macrophages and cancer cell-derived factors.
Main Results:
- CS exposure significantly increased lung tumor proliferation in wild-type mice but not in CRAMP-deficient mice.
- CS induced CRAMP-dependent myeloid cell recruitment into lung tumors.
- Impaired recruitment of CRAMP-positive cells was observed in myeloid cell-specific RelA/p65 knockout mice.
- LL-37/hCAP-18 in macrophages was induced by soluble factors from cancer cells in vitro.
Conclusions:
- Cathelicidin expressed by myeloid cells promotes cigarette smoke-induced lung tumor growth.
- This promotion occurs through the enhanced recruitment of inflammatory cells into the tumor microenvironment.
- Myeloid p65/RelA and tumor cell-derived soluble factors are critical regulators of cathelicidin expression in this context.
