Abstract 3880: Exploring the role of up-regulated genes in highly metastatic oral cancer subline using spontaneous metastatic mouse model.

Abstract

Abstract Metastasis is one of the critical factors contributing to poorer prognosis and QOL in cancer patients. Although this mechanism has been gradually revealed, there are few genes found as useful diagnostic markers or molecular targets for clinical application so far. In this study, we attempted to establish in vitro/in vivo metastatic models using a human oral squamous cell carcinoma cell lines (HOC313). We first carried out in vivo selection of high-metastatic tumor cells by means of sequential subcutaneous (s.c.) implantation (1×107 cells) of this cell line into SCID mice, resulting in the establishment of a highly metastatic subline which metastasized to axillary lymph nodes and lung. Moreover, we developed the imaging system using parent cells and highly metastatic cells. Then, to explore metastasis-related genes and signaling pathways, we performed integrative analyses using array CGH, cDNA microarray and the systems biological approach based on their data sets. Then we identified copy number aberrations (CNAs) of chromosome 19 and differentially expressed genes between parent cells and high-metastatic cells. Up regulated genes in high-metastatic cells are related with cell growth, migration, invasion and metastatic ability. Among these, one gene was closely associated with migration, invasion and metastasis. Moreover, when knocking down of this gene, we observed morphological change from mesenchymal phenotype to epithelial phenotype. Further analyses of these genes may ultimately lead to the development of novel modalities of diagnosis and therapy for cancer metastasis. Citation Format: Tomoki Muramatsu, Ken-ichi Kozaki, Seiya Imoto, Rui Yamaguchi, Satoru Miyano, Johji Inazawa. Exploring the role of up-regulated genes in highly metastatic oral cancer subline using spontaneous metastatic mouse model. [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 3880. doi:10.1158/1538-7445.AM2013-3880