Osteopontin Regulates VEGFA and ICAM-1 mRNA Expression in Breast Carcinoma.

Abstract

To analyze the regulatory role of osteopontin on biomarkers associated with cell survival, invasiveness, and angiogenesis mechanisms in a clinical series and breast cancer cell lines. We analyzed by quantitative real-time polymerase chain reaction the messenger RNA (mRNA) expression of osteopontin, Bcl2, intercellular adhesion molecule 1 (ICAM-1), and vascular endothelial growth factor A (VEGFA) in several breast cancer cell lines and in 148 breast carcinomas classified into intrinsic subtypes. We found coexpression of osteopontin, Bcl2, ICAM-1, and VEGFA in triple-negative MDA-MB-468 and MDA-MB-231 cell lines. Furthermore, osteopontin silencing by small interfering RNA inhibited ICAM-1 and VEGFA expression and cell proliferation in MDA-MB-468 cells. In breast cancer specimens, we found a positive correlation between osteopontin, ICAM-1, and VEGFA mRNA expression, especially in triple-negative/basal-like tumors. Among patients with osteopontin-overexpressing tumors, VEGFA remained an independent prognostic indicator for recurrence (hazard ratio, 2.95; 95% confidence interval [CI], 1.48-5.87; P = .002) and death (hazard ratio, 3.25; 95% CI, 1.48-7.11; P = .003) (multivariate analysis, Cox regression). Our results support that osteopontin regulates ICAM-1 and VEGFA expression mainly in triple-negative/basal-like breast carcinomas, suggesting a relevant role in the pathogenesis and tumor progression of this molecular subtype. Moreover, VEGFA mRNA levels showed an independent prognostic value in patients with breast cancer.