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Am. J. Respir. Crit. Care Med., Volume 160, Number 4, October 1999, 1269-1273

Vascular Endothelial Growth Factor and Osteopontin in Stage I Lung Adenocarcinoma

NORIHARU SHIJUBO, TOSHIMITSU UEDE, SHIGEYUKI KON, MASAHIRO MAEDA, TATSUYA SEGAWA, AKIHIRO IMADA, MICHIO HIRASAWA, and SHOSAKU ABE

Third Department of Internal Medicine, Sapporo Medical University School of Medicine, and Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University, Sapporo; and Immuno-Biological Laboratories, Fujioka, Japan

Tumor growth and metastasis are angiogenesis-dependent processes initiated and regulated by a number of cytokines. Vascular endothelial growth factor (VEGF) is a potent angiogenic protein with a selective mitogenic effect on vascular endothelial cells. Osteopontin (OPN) induces endothelial cell migration and upregulates endothelial cell migration induced by VEGF. To clarify the cooperative role of VEGF and OPN in tumor angiogenesis, we stained VEGF, OPN, and CD34 immunohistochemically in 87 cases of stage I non-small cell lung cancer (adenocarcinoma, 55, and squamous cell carcinoma, 32). Of the 87 patients studied, 27 patients had postoperative relapse and 60 patients did not. VEGF was found in 34 of 55 cases of adenocarcinomas and 14 of 32 squamous cell carcinomas, and OPN was found in 30 of 55 adenocarcinomas and 10 of 32 squamous cell carcinomas. In adenocarcinoma, microvessel counts of VEGF-positive and OPN-positive tumors were significantly higher than VEGF-negative and OPN-negative tumors, respectively, whereas in squamous cell carcinoma they were not. More importantly, patients with VEGF- and OPN-positive stage I lung adenocarcinoma had significantly worse prognosis as compared with other groups. Cooperation of OPN is important in VEGF-mediated tumor angiogenesis in stage I lung adenocarcinoma.




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