Abstract 5129: AGR2 is a potential marker for metastatic human oral squamous cell carcinoma.

Abstract

Abstract Purpose: The mortality of oral cancer, which is a common subtype of human and neck squamous cell carcinomas (HNSCC), is increasing in Taiwan, Southeast Asia, and eastern countries during the last twenty years. Averagely, the 5-year survival rate of distant metastasis of oral carcinoma is less than 30-40%. Prevention of cancer metastasis to distant organs is one of practical approaches that may reduce the mortality of patients. This study aims to identify novel metastatic tumor markers for oral cancer. Experimental Design and Results: A high metastatic sub-population, HSC-3-5 cells, was divided from human oral cancer HSC-3 by Transwell invasion assay. Our results indicated that HSC-3-5 cells exhibited higher metastatic capacities due to re-arrangement cytoskeleton and subsequently epithelial mesenchymal transition transformation in vitro. In addition, metastatic and tumorigenetic capacities of HSC-3-5 cells were characterized by spontaneous and experimental metastasis experiments in vivo. The microarray-based gene expression profiles of HSC-3/HSC-3-5 cells and their corresponded xenografts (orthotropic and heterotopic) were then performed. Anterior gradient 2 (AGR2), a pro-oncogenic signaling intermediate in various human cancers, was the most significantly up-regulated gene in HSC-3-5 cells compared with HSC-3. Furthermore, overexpression of AGR2 protein was verified in cells, xenograft animal models, and clinical patient tissues, and it encompassed positive relation with OSCC metastasis. Conclusions: A high metastatic sub-population HSC-3-5 cell line derived from human oral cancer HSC-3 cells was divided. HSC-3-5 cells represented higher capacities not only in metastasis but also in tumorigenesis. According to microarray gene profiles and immunohistochemistry analysis, the expression of identified potential biomarker, AGR2, showed positive relationship with tumor metastasis during oral carcinogenesis. Citation Format: Yi-Ting Chen, Chung-Liang Ho, Po-Ku Chen, Yuh-Ling Chen, Chung-Fa Chang. AGR2 is a potential marker for metastatic human oral squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5129. doi:10.1158/1538-7445.AM2013-5129