Osteopontin as a potential biomarker of proliferation and invasiveness for lung cancer

Abstract

Lung cancer is one of the most malignant tumors and poses a significant threat to human health. Osteopontin (OPN) is a variably expressed, secreted glycophosphoprotein that mediates the growth and metastases of several carcinoma types. In this study, we aimed to understand the role of OPN in lung cancer cell proliferation and invasiveness. Expression of OPN was examined using an immunohistochemical method in paraffin-embedded sections collected from 49 patients with lung cancer. We silenced OPN expression by lentivirus-mediated OPN-specific small interfering RNA (siRNA) and examined the proliferation and invasiveness of OPN-silenced lung cancer cell (A549) through MTT, BrdU, flow cytometry, and Matrigel assay. In addition, we tested the role of individual OPN splice variants in A549 cell growth and invasion by constructing OPN overexpression lentiviruses. Downregulation of OPN inhibited A549 cell proliferation and in vivo tumor growth, abrogated augmentation of invasion, induced G1-phase cell cycle arrest, and induced cell late apoptosis and necrosis. Moreover, the proliferation and invasiveness was linked to different OPN splice variants, of which OPN-b affected the cell proliferation and OPN-c showed significant correlation with invasion behavior. Our data suggested that OPN served as a potential biomarker for invasive lung cancer and provided new molecular-targeted therapy for lung cancer based on lentivirus-mediated RNA interference.