IGFBP-3 suppresses tumor growth and angiogenesis in NSCLC xenografts and vascular endothelial cells. (A) H1299 xenograft tumor growth (left) 10 days after injection with IGFBP-3–expressing adenoviruses (Ad-BP-3) or empty viruses (Ad-EV). Tumor growth is expressed as the mean ± SEM. An immunohistochemical analysis of CD31 (right) was performed in xenograft tissues, and the number of CD31-immunoreactive vessels per high-power field was counted. The results represent the mean calculated from 5 mice (bars, SDs). *P < .05 compared with the control group. Representative CD31 immunostaining in H1299 xenograft tissues is included. (B) Matrigel plug assay with A549 cells. Gross observed results of blood vessels are expressed as the mean of 5 tumors ± SEM, **P < .01. (C-D) Effect of CM from indicated NSCLC cell lines that had been infected with Ad-EV or Ad-BP-3 (C-D) or treated with rBP-3 (E-F) on HUVEC proliferation (C,E), chick aortic sprouting (D), and HUVEC tube formation (F). The results represent the means (bars, SDs) of 5 identical wells. *P < .05; **P < .01; ***P < .001.