p53 suppresses CCL2-induced subcutaneous tumor xenograft

Abstract

Chemokine (C-C motif) ligand 2 (CCL2) has recently been found to be a key player in the pathology of many human glomerular and tubulointerstitial diseases. CCL2 has also been found to be expressed in various cancers, including human hepatoma cells, human cancer progression, and human multiple myeloma cells. Thus, the inhibition of elevated CCL2 production may provide a new avenue for therapeutic intervention in CCL2-mediated cancer diseases. A previous study has indicated that knockdown of human p53 has a strong negative impact on CCL2 induction. We therefore are interested in how p53 regulates CCL2 gene expression. In the following study, our findings indicate that p53 binds to CCL2, consequently significantly downregulating CCL2 promoter activity. Furthermore, injection of CCL2-promoting cancer cells (CCL2/A549) in p53-deficient mice for 3 weeks strongly induced subcutaneous xenograft tumor growth compared with the control. Overall, the research results support the novel role of p53 in suppression of chemokine (such as CCL2)-mediated cancer diseases.