![]() These controversial findings regarding the role of LL-37/CRAMP and its receptor FPR2 in different cancer models imply that the mechanism of action of FPR2-dependent immune modulation during tumor progression still needs to be elucidated. have documented that upon the stimulation with Lewis lung carcinoma cell supernatant, macrophages from FPR2 deficient mice results in M2 phenotype by phosphorylation of STAT3 and STAT6 ( 12). However, in contrast to this report, Wang et al. have shown that receptor for CRAMP, formyl peptide receptor 2 (FPR2), expressed on human macrophages polarizes them into protumorigenic type 2 macrophages (M2) by upregulating monocyte chemoattractant protein-1 (MCP-1) and macrophage colony stimulating factor (M-CSF) partially depending on NF-κB pathway in human hepatocellular carcinoma model ( 9). The overexpression of LL-37/CRAMP correlates with increased chemotaxis of CD45 + leukocytes and mesenchymal stromal cells in human ovarian cancer and CD68 + myeloid cells in cigarette smoke-induced mouse models of lung cancer ( 6, 10, 11). Recently, elevated level of LL-37/CRAMP has been documented in epithelial carcinomas of ovary, breast, and lung ( 6– 10). Originally, LL-37/CRAMP is known as an important effector molecule of innate immunity that provides a first-line host defense system by chemoattracting and activating the innate immune cells including neutrophils and macrophages to the inflammatory sites ( 3– 5). ![]() Previously, we have shown a positive correlation between the expression of antimicrobial peptide (AMP), human leucine leucine 37 (LL-37) and its mouse orthologue cathelicidin-related AMP (CRAMP), and the grade of tumor in both human and mouse PCa ( 2). Progression of prostate cancer (PCa) is associated with protumorigenic immune modulation ( 1). To identify mechanisms CRAMP function, macrophage colony stimulating factor (M-CSF) and monocyte chemoattractant protein 1 (MCP-1) gene expression was analyzed by QRT-PCR and STAT3 signaling was determined by immunoblotting. To differentiate protumorigenic events mediated by tumor-derived CRAMP from host immune cell-derived CRAMP, tumor challenge study was performed in CRAMP-deficient mice. The role of CRAMP in differentiation and polarization of immature myeloid progenitors (IMPs) to protumorigenic type 2 macrophages (M2) in TME was determined by adoptive transfer of IMPs into mice bearing CRAMP (+) and CRAMP (−) tumors. CRAMP-mediated chemotaxis of different innate immune cell types to the tumor microenvironment (TME). To investigate protumorigenic role(s) of cathelicidin-related antimicrobial peptide (CRAMP), a murine orthologue of LL-37, the present study compared tumor growth kinetics between mouse PCa cell lines with and without CRAMP expression (TRAMP-C1 and TRAMP-C1 CRAMP-sh, respectively) in immunocompetent mice.
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