Co-expression of immunoglobulin-like transcript 4 and angiopoietin-like proteins in human non-small cell lung cancer

摘要

The development of strategies for the inhibition of non-small cell lung cancer (NSCLC) progression and metastasis have been mainly unsuccessful, in part due to insufficient mechanistic understanding of the disease. In the current study, the critical role of the co-expression of immunoglobulin-like transcript 4 (ILT4) and its ligands, angiopoietin-like proteins (ANGPTLs), in the development of NSCLC was demonstrated. ILT4 and ANGPTL2 or ANGPTL5 were found to be co-expressed in the five NSCLC cell lines that were investigated at the mRNA and protein level. Upon up- or downregulation of ILT4, the expression of ANGPTL2 was increased or reduced, respectively, while the expression of ANGPTL5 was unaffected. The co-expression of ILT4 and ANGPTL2/ANGPTL5 was detected in human primary NSCLC tissues using immunohistochemical analysis. In total, 114 lung cancer specimens were included in the study; high expression of ILT4, ANGPTL2 and ANGPTL5 was observed in 58.8, 45.6 and 55.3%, respectively. The expression of ILT4 was found to be significantly correlated with a high expression level of ANGPTL2 (R=0.466, P=0.004); however, it was not correlated with the expression of ANGPTL5 (R=0.142, P=0.131). In ILT4-positive samples, cases with ANGPTL2-positive expression levels presented greater levels of lymph node metastasis (P=0.011) and shorter overall survival times (P=0.045). In addition, cases with ANGPTL5-positive expression presented poor overall survival rates (P=0.040). By contrast, in the ILT4-negative cases, no statistically significant differences were identified in the overall survival rates between samples with high and low expression of ANGPTL2 or ANGPTL5. In conclusion, the present study demonstrated the presence of interaction among ILT4 and ANGPTLs, which may be important in NSCLC progression. Therefore, the blockade of ANGPTLs or ILT4 may be an effective therapeutic approach for NSCLC treatment.