Abstract 2178: Serial analysis of gene expression (SAGE) of esophageal squamous cell carcinoma: ADAMTS-16 is up-regulated in esophageal squamous carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. To identify potential targets for diagnosis and therapeutics of ESCC, we performed Serial Analysis of Gene Expression (SAGE) on the ESCC sample. We generated the SAGE library from one ESCC sample and obtained a total of 14,430 tags, including 5,765 that were unique. By comparing SAGE tags from ESCC samples with those from normal human squamous esophagus (Gene Expression Omnibus accession number, GSM52501), we found several genes and tags that were differentially expressed between ESCC and normal squamous esophagus. Among these, we focused on the ADAM metallopeptidase with thrombospondin type 1 motif, 16 (ADAMTS16) gene. ADAMTS has been described as part of a family of zinc dependent proteases (metzincin family), which play important roles in a variety of normal and pathological conditions including arthritis and cancer. Although ADAMTS16 is expressed in some organs, the relationship with cancers, including ESCC, has not been studied. Quantitative reverse transcription-polymerase chain reaction analysis showed a high level of ADAMTS16 expression in 8 out of 20 ESCC samples (40%) but not in 15 kinds of normal tissues. We also investigated the mRNA expression levels of SCCA1, which encodes SCC antigen. High levels of SCCA1 mRNA expression were found in 4 of 20 cases (20%). We then investigated the relation of ADAMTS16 expression to clinicopathologic characters and found that ADAMTS16 overexpression correlated with the advanced T grade (p = 0.0215). Western blot analysis revealed that ADAMTS16 protein expression was detected in all 4 ESCC cases, whereas in 1 of the 4 corresponding non-neoplastic mucosa. Furthermore, ADAMTS16 protein was detected in culture media from the TE5 ESCC cell line which expressed significant level of ADAMTS16 mRNA, indicated that ADAMTS16 is surely secreted. To evaluate the biological significance of ADAMTS16 in ESCC, we performed MTT assay and transwell invasion assay. These examination revealed that knockdown of ADAMTS16 by siRNA in TE5 cells inhibited both cell growth and invasion ability. These results suggest that ADAMTS16 has a high potential as a serum tumor marker and therapeutic target for ESCC. 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 2178.