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 < 0.0088, <0.0008, and 0.0305, respectively; Fisher's exact method). The localizations of Ang-1, Ang-2, and TIE2 were confirmed within tumor cells immunohistochemically. Vascular number and measurement area were significantly higher in the IL-10-positive NSCLCs (33.500 +/- 9.299/microm(2) and 4.742 +/- 1.287%) as compared with IL-10-negative NSCLCs (10.611 +/- 2.839/microm(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.
Hatanaka
H
H
Department of Pathology, Tokai University School of Medicine, Kanagawa 259-1193, Japan.
Abe
Y
Y
Naruke
M
M
Tokunaga
T
T
Oshika
Y
Y
Kawakami
T
T
Osada
H
H
Nagata
J
J
Kamochi
J
J
Tsuchida
T
T
Kijima
H
H
Yamazaki
H
H
Inoue
H
H
Ueyama
Y
Y
Nakamura
M
M
D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D042702:Angiopoietin-2; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000378:metabolism; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053701:Receptors, Interleukin-10; D029701:Saccharomyces cerevisiae Proteins; D013223:Statistics as Topic; D019699:Thrombospondins / Q000378:metabolism; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099262:Thrombospondin 2
D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D042702:Angiopoietin-2; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D016753:Interleukin-10; D008222:Lymphokines; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D029701:Saccharomyces cerevisiae Proteins; D019699:Thrombospondins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099262:Thrombospondin 2; C468226:ADGRB1 protein, human; C101206:SUB1 protein, S cerevisiae