Abstract 3587: Protein S100A10: Expression and correlation with sensitivity to oxaliplatin in colorectal cancer cells

Abstract

Abstract Introduction: Oxaliplatin (L-OHP) is a key drug in colorectal cancer (CRC) treatment. However, the individual response to L-OHP-based chemotherapy is still unpredictable. We previously found that S100A10 is a potential biomarker for predicting L-OHP sensitivity by using proteomic analysis (Suzuki, S. et al., AACR, # 2894, 2009). Here, we aimed to determine the specificity of S100A10 as a predictive candidate biomarker for L-OHP sensitivity and investigate the expression and role of S100A10 in regulating L-OHP sensitivity in human CRC cell lines. Experimental Procedures: To determine the specificity of S100A10 in predicting L-OHP sensitivity, we investigated a correlation between S100A10 protein expression levels and L-OHP or 5-fluorouracil (5-FU) sensitivity (IC50 value) in 8 human CRC cell lines: COLO320, DLD-1, HCT-15, HCT116, HT-29, LS174T, SW480, and SW620. The protein expression profiles of S100A10 and annexin A2-a binding partner of S100A10-were analyzed in cell lysates by western blotting. We used RNA interference to investigate whether S100A10 can directly regulate L-OHP sensitivity. HT-29 cells were transfected with siRNA against S100A10 or/and annexin A2. Cells were treated with L-OHP 72 h after transfection, when knockdown of target molecules was confirmed. Cell viability was assessed using crystal violet dye. To determine extracellular secretion of S100A10, serum-free conditioned medium incubated with the cells for 24 h was analyzed by western blotting. Results and Discussion: The intracellular S100A10 protein levels were not correlated with 5-FU sensitivity (p = 0.199, r = 0.272) but were significantly correlated with L-OHP sensitivity (p = 0.008, r = 0.529), indicating that S100A10 can be a specific predictive biomarker for L-OHP sensitivity. The effect of S100A10 knockdown on cell viability after L-OHP exposure was marginal. Annexin A2 knockdown markedly reduced both intracellular annexin A2 and S100A10 proteins and tended to lower cell viability. In addition, intracellular S100A10 protein expression levels were strongly correlated with annexin A2 in the 8 CRC cell lines. One possible explanation for S100A10 involvement in L-OHP chemosensitivity is the contribution toward cell viability partly regulated by annexin A2, suggesting that intracellular handling of S100A10 may be important. In addition, S100A10 was found to undergo extracellular secretion. Thus, S100A10 shows promise as a surrogate and noninvasive biomarker for sensitivity to L-OHP. Conclusions: S100A10 can serve as a potential biomarker to predict L-OHP sensitivity, not 5-FU sensitivity. The intracellular handling of S100A10, partly associated with annexin A2, may help elucidate the biological mechanisms involved in mediating cancer cell viability after exposure to L-OHP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3587.