Significant Correlation between Interleukin 10 Expression and Vascularization through Angiopoietin/TIE2 Networks in Non-small Cell Lung Cancer

The expression of interleukin 10 (IL-10) is correlated with clinical prognosis in non-small cell lung cancer [NSCLC (H. Hatanaka et al. , Ann. Oncol., 11: 815–819, 2000)]. However, the effects of IL-10 expression on vascularization in NSCLC are not apparent. We examined the gene expression of IL-10/IL-10 receptor and various angiogenic/angioinhibitory factors in 95 NSCLC samples to determine the correlation between IL-10 production and vascularization. Vascular endothelial growth factor, angiopoietin [ Ang ( Ang-1 and Ang-2 )], thrombospondin, brain-specific angiogenesis inhibitor 1, vascular endothelial growth factor receptors ( KDR and flt-1 ), and Ang receptor ( TIE2 ) gene expression were evaluated by reverse transcription-PCR. The cellular localization of these factors and vascularity in the cancer stroma were examined immunohistochemically. Seventy-eight (82.1%) and 93 (97.9%) of these 95 NSCLCs were positive for IL-10 and IL-10 receptor, respectively. Ang-1 , Ang-2 , and TIE2 gene expression was seen in 76 (97.4%), 73 (93.6%), and 78 (100%) of 78 IL-10-positive NSCLCs, respectively, and was significantly correlated with IL-10 gene expression ( P IL-10 -positive NSCLCs (33.500 ± 9.299/μm 2 and 4.742 ± 1.287%) as compared with IL-10 -negative NSCLCs (10.611 ± 2.839/μm 2 and 0.718 ± 0.331%; Mann-Whitney U test, P = 0.0039). The IL-10 expression did not show any significant correlation with the expression of other factors. These results suggested that tumor-produced IL-10 promotes stromal vascularization through expression of Ang-1, Ang-2, and TIE2.