P2.03b-091 CD47 Promotes Tumor Invasion and Metastasis in Non-small Cell Lung Cancer: Topic: Biomarkers

Abstract

CD47 is overexpressed in many human cancers and its level positively correlates with tumor invasion and metastasis. However, little is known on the expression and biological significance of CD47 in human non-small cell lung cancer (NSCLC). In this study, we measured the expression level of CD47 in NSCLC tissues and cell lines, and examined its correlations with different clinicopathologic parameters. The functional significance of CD47 in NSCLC migration/invasion was analyzed both in vitro and in vivo. The biological importance of Cdc42 in this process was evaluated. CD47 was significantly up-regulated in NSCLC cell lines and tumor tissues than in matched tumor-free control tissues. Increased CD47 expression correlated with clinical staging, lymph node metastasis and distant metastasis. To understand the biological significance of CD47, we applied both gain-of-function and loss-of-function approaches in NSCLC cell lines. The siRNA-mediated down-regulation of CD47 inhibited cell invasion and metastasis in vitro, while the overexpression of CD47 by plasmid transfection generated the opposite effects. In vivo, CD47-specific shRNA significantly reduced tumor growth and metastasis. On the molecular level, the expression of CD47 correlated with that of Cdc42 both in the cell lines and NSCLC specimens. Inhibition of Cdc42 attenuates the invasion and metastasis of CD47-overexpressing cells. Our findings provide the first evidence that CD47 is an adverse prognostic factor for NSCLC progression and metastasis, and thus a promising therapeutic target. Cdc42 is a downstream mediator of CD47-promoted metastasis.