Abstract 3061: Tumor suppressive and angiogenic role of THSD1 in esophageal squamous cell carcinoma and nasopharyngeal carcinoma

Background and aims: Loss of chromosome 13q regions is a frequent event in both esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). By microcell-mediated chromosome transfer, chromosome 13 was demonstrated to play a significant tumor suppressive role in both ESCC and NPC in our laboratory. THSD1 is a novel candidate tumor suppressor gene (TSG) previously identified by microarray differential gene expression profiling. It encodes a transmembrane molecule containing a thrombospondin type 1 repeat (TSR), which may be involved in cell adhesion and angiogenesis. Proteins possessing the TSR, such as thrombospondin-1 (Tsp1), ADAM metallopeptidase with thrombospondin type 1 motif, 1 (ADAMTS1) and ADAMTS8, regulate angiogenesis. We previously showed that the mechanisms for THSD1 silencing in ESCC involved loss of heterozygosity and promoter hypermethylation. Our preliminary data indicated transfection of wild type THSD1 into an ESCC cell line, SLMT-1, resulted in significant reduction of colony-forming ability, hence providing functional evidence for its growth suppressive activity. The current study aims to examine if THSD1 plays a significant tumor suppressive role in the nude mouse tumorigenicity assay and to elucidate the mechanism(s) involved in tumor suppression. Methods: Transfection by lipofection of both variants of THSD1 into the ESCC SLMT-1 and NPC HONE1-2 cell lines was used to study the effect of THSD1 in tumor suppression and anti-angiogenesis. Results: Quantitative RT-PCR detected down-regulation of THSD1 expression in 36.4% (16/44) primary ESCC and 54.5% (12/22) NPC tissues. Nude mouse tumorigenicity assays showed tumor suppression in THSD1 over-expressing clones in both ESCC and NPC. Flow cytometry analysis showed over-expression of THSD1 resulted in endoreplication. Tube formation assay with HUVEC is underway to examine the angiogenic role of THSD1. Conclusions: THSD1 is a promising candidate TSG in both ESCC and NPC. 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 3061.