The RAGE ligand, S100P, has increased expression in colon cancer

Abstract

Abstract Introduction: Colon cancer is the third most prevalent cancer in the United States. However, the molecular mechanisms involved in the development and progression of colon cancer are poorly understood. In the current study, we investigated the role of S100P, a RAGE ligand, in human colon cancer cell function. Methods: RT-PCR and western blot were performed for detection of RAGE and S100P in colon cancer tissue with matched normal colon as well as colon cancer cell lines. Functional studies were conducted in the colon cancer cell line SW480, which expresses RAGE but not S100P. The influence of S100P on colon cancer was evaluated by exogenously adding purified S100P in order to analyze Erk phosphorylation, cell proliferation, and migration. Results: While RAGE was expressed equally in both normal and cancerous colon samples, S100P had increased expression in cancer. Adding exogenous S100P to SW480 cells for 30 minutes stimulated phosphorylation of Erk1/Erk2 by 2-fold. Treatment of SW480 cells with purified S100P (100 nM) resulted in increased proliferation over the control by 40 ± 12% at 48 hrs. SW480 cell migration rate was increased by 547 ± 24% of control, observed with 100nM S100P. Conclusions: These data indicate that S100P is expressed at greater levels in colon cancer than normal tissue, and that S100P stimulates colon cancer cell growth, Erk phosphorylation, and motility in vitro. Therefore, this molecule or its receptor may be a novel target for the development of new therapies.