Abstract A184: Knock-down of Cripto-1 expression by small interfering RNA inhibits growth and migration of oral squamous cell carcinoma cells.

Abstract

Abstract Background: Cripto-1, also known as teratocarcinoma-derived growth factor-1 (TDGF-1), is a member of the EGF-CFC family. Cripto-1 has been found to be overexpressed in different human carcinomas, including breast, colon, lung, cervix, stomach, pancreas, and nasopharynx, while it was absent or very low in normal adult tissue. In vitro and in vivo studies have shown that Cripto-1 plays an important oncogenic role during carcinogenesis by promoting cell proliferation, migration, invasion, and tumor angiogenesis, as well as inducing the epithelial-to-mesenchymal transition. In our previous study, we first demonstrated that Cripto-1 protein was significantly overexpressed in oral squamous cell carcinoma (OSCC) tissues than in normal oral mucosa and the exogenous recombinant human Cripto-1 protein induced a significant increase in the cell proliferation and migration of OSCC cell lines (SCC-4 and SCC-25). Our data suggested that Cripto-1 may be involved in the tumorigenesis and progression of OSCC. To validate the value of Cripto-1 as a novel molecular target for OSCC treatment, in the present study, we investigated whether the suppression of endogenous Cripto-1 inhibits the growth and migration of OSCC cells. Methods: We screened 13 OSCC cell lines to select cell lines with high Cripto-1 expression by RT-PCR and western blot analysis. Among them, KOSCC-33A and HSC4 cell lines were selected and transfected with anti-Cripto-1 siRNA and negative control siRNA. Cell proliferation was evaluated 24h, 48h, and 72h after transfection, and migration assay was also performed 24h and 48h after transfection, with anti-Cripto-1 siRNA and negative control siRNA. Statistical significance was determined using t-test. Results: The results of RT-PCR analysis revealed that the Cripto-1 mRNA in KOSCC-33A and HSC4 cells were effectively suppressed by anti-Cripto-1 siRNA when compared with cells treated with a negative control siRNA. In the cell proliferation assay, we found that Cripto-1 knock-down induced a significant inhibition of the growth of KOSCC-33A and HSC4 cells (P <0.05). In addition, Cripto-1 knock-down resulted in a significant decrease in the migration of both cell lines (P <0.05). Conclusion: The present study confirms that Cripto-1 plays an important role in the growth and motility of OSCC cells. Our data also suggest that suppression of Cripto-1 expression may be one of the new strategies for the treatment of OSCC. Further studies are in progress to clarify the signaling pathway underlying the oncogenic effects of Cripto-1 in OSCC. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A184. Citation Format: Ji-Hoon Kim, Young-Ah Cho, Ji-Soo Hong, Eun-Jin Choi, Seong-Doo Hong, Jae-Il Lee, Sam-Pyo Hong, Hye-Jung Yoon. Knock-down of Cripto-1 expression by small interfering RNA inhibits growth and migration of oral squamous cell carcinoma cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A184.