Significance of expression of TGF-beta in pulmonary metastasis in non-small cell lung cancer tissues.
Recent studies have evaluated the cytokine network involved in the local immune response to tumors. In addition to infiltrating inflammatory cells, tumors also produce cytokines and growth factors that may alter tumor growth and tumor immunogenicity. Ninety-one samples of NSCLC were used in this study. We measured the expression of VEGF, TNF-alpha, TGF-beta, IL-6, IL-8, IL-12, INF-gamma, and MCP-1 in NSCLC tissues, by ELISA. The expression of IL-6 and IL-8 were significantly higher in squamous cell carcinoma than in adenocarcinoma (p=0.016 and p<0.001, respectively). The expression of TGF-beta, MCP-1 and IL-8 were significantly higher in pulmonary metastasis positive than negative cases (p=0.002, p=0.001, and p=0.008, respectively). In multivariate logistic regression analysis, the expression of TGF-beta was an independent risk factor for the occurrence of pulmonary metastasis (p=0.008, 95% CI=1.002-1.011). We confirmed that tumor infiltrating stromal cells were major sources of TGF-beta by immunohistochemical analysis. The expression of VEGF and IL-8 were significantly higher in cases with central necrosis (p=0.006 and p=0.011, respectively). We speculated that TGF-beta expression in tumor infiltrating stromal cells may regulate the occurrence of spontaneous pulmonary metastasis in NSCLC. (Ann Thorac Cardiovasc Surg 2003; 9: 295-300)
Saji
Hisashi
H
Pulmonary Oncology Unit, Department of Surgery, Tokyo Medical University, Tokyo, Japan.
Nakamura
Haruhiko
H
Awut
Idiris
I
Kawasaki
Norihito
N
Hagiwara
Masaru
M
Ogata
Akihiko
A
Hosaka
Makoto
M
Saijo
Takamoto
T
Kato
Yasubumi
Y
Kato
Harubumi
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000556:secondary*; D046508:Culture Techniques; D016207:Cytokines / Q000032:analysis* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D016015:Logistic Models; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011336:Probability; D011379:Prognosis; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D016212:Transforming Growth Factor beta / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D014408:Biomarkers, Tumor; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D018664:Interleukin-12; D007371:Interferon-gamma