[Mechanisms of antimicrobial peptide cathelicidin secreted by non-tumorous cells for lung tumor growth].

ABSTRACT

OBJECTIVE: To investigate the effect of antimicrobial peptide cathelicidin secreted by non-tumorous cells in lung tumor growth. METHODS: CRAMP(-/-) mice and WT mice were used to establish a lung cancer model via tail vein injection of Lewis lung carcinoma cells (LLC1). Lung was weighted and tumor number on the lung surface was counted. Kaplan-Meier (K-M) survival curve was used to analyze survival rate of mice. Expression of cathelicidin, Ki-67 and CD68 in the tumor tissue was measured by immunohistochemical analysis. BALF cells were stained with Diff Quik and percentages of leukocyte types were determined by light microscopy. RESULTS: Cathelicidin was high expression in inflammatory cells of tumor tissue, whereas weak expression in tumor cells. The lung weight and number of tumor in CRAMP-/- mice were (0.25±0.04)g and (9.60± 2.25), respectively, which were significantly lower than those of WT mice (0.65±0.05) g and (23.40± 2.68). The difference was statistically significant (t=6.07, 3.95, all P<0.05). And Kaplan-Meier survival analysis showed median survival time of CRAMP-/- mice was 49(46-51)d, which was longer than 34(28-39) d of WT mice (χ2=12.00, P<0.05). And the positive rate of Ki-67 tumor cells was significant reduced from (35.80±2.96)% in WT mice to (18.80±2.38)% in CRAMP-/- groups (t=4.48, P<0.05). The total cell number as well as the number of lymphocytes, neutrophils, and macrophages in BALFs of CRAMP-/- mice were (4.72±0.86)×10(4), (0.08±0.02)×10(4), (0.05±0.02)×10(4) and (4.60±0.84)×10(4), respectively, while of WT mice were (16.18±1.61)×10(4), (0.32±0.05)×10(4), (0.20±0.05)×10(4) and (15.66±1.57)×10(4). All of them had significant difference (t=6.28, 4.39, 3.00, 6.20, all P<0.05). In addition, the infiltration of macrophages into lung tumors was decreased in CRAMP-/- mice compared to WT mice, from (15.53±2.28)/high power field to (6.77±3.12)/high power field (t=3.41, P<0.05). CONCLUSIONS: Non-tumor cells secreted cathelicidin promotes tumor cell proliferation and lung tumor growth. Recruitment of inflammatory cells such as macrophages into the tumor microenvironment may be the main mechanism of action.