Abstract #1251: CXCL12 and its receptors CXCR4 and CXCR7 as potential molecular targets for lung cancer

Abstract

The interaction between the chemokine CXCL12 and the two receptors, CXCR4 and CXCR7, is thought to play a role in tumor growth and metastasis in human cancers. However, the expression of CXCL12, CXCR4 and CXCR7 and their role in lung cancer is not fully elucidated. Here we examined the expression of CXCL12, CXCR4 and CXCR7 in 23 small cell lung cancer (SCLC) cell lines and 32 non-small cell lung cancer (NSCLC) cell lines. CXCL12, CXCR4 and CXCR7 were overexpressed in lung cancer cell lines compared with human non-malignant lung epithelial cells (N=6). CXCR4 levels were significantly higher in SCLCs than those in NSCLCs, while there were no differences in the levels of both CXCL12 and CXCR7 between SCLCs and NSCLCs. Frequencies of CXCL12, CXCR4 and CXCR7 overexpression were 45%, 80% and 16%, respectively, and CXCL12 expression was positively associated with expression of CXCR4 and CXCR7. RNA interference-mediated CXCL12 knockdown inhibited cell growth and migration in a CXCL12-overexpressing lung cancer cells, and the effect involved inactivation of the MEK-ERK pathway. Furthermore, treatment with an anti-CXCL12 neutralizing antibody inhibited cell growth in four of CXCL12-overexpressing lung cancer cell lines but not in CXCL12 non-expressing lines. The results demonstrate that: CXCL12, CXCR4 and CXCR7 are concomitantly overexpressed in lung cancers; CXCR4 is abundantly expressed in SCLCs compared with NSCLCs; and that CXCL12 is required for lung cancer cell growth and migration via the MEK-ERK signaling pathway. Thus, inhibition of CXCL12 activity could be a novel therapeutic approach in lung cancer.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1251.