Abstract 3058: ADAMTS9 inhibits angiogenesis and induces apoptosis in nasopharyngeal carcinoma

Abstract

Abstract Background and aims: A disintegrin-like and metalloprotease with thrombospondin type 1 motif 9 (ADAMTS9), a gene mapping to 3p14.2, has been shown to be silenced by promoter hypermethylation in nasopharyngeal carcinoma (NPC). The ADAMTS family consists of 19 secretion protein members consisting of a disintegrin domain, metalloproteinase domain, and different numbers of thrombospondin type 1 motifs. ADAMTS9 encodes a member of a large family of 19 metalloproteases involved in maturation of precursor proteins, extracellular matrix remodeling, cell migration, and inhibition of angiogenesis. Although the related matrix metalloproteases and ADAM proteases have been clearly implicated in tumor progression and angiogenesis, the role of ADAMTS proteases in cancer is less clearly defined. In the present study, we investigated the in vivo and in vitro functional roles of ADAMTS9 in angiogenesis of NPC. Methods: To examine the antigiogenic activity of ADAMTS9 in NPC, the in vivo gel plug and in vitro tube formation assays were performed using a tetracycline-regulated expression vector in the present study. Results: Here we show that when incubated with conditional media from the ADAMTS9 stable transfectant, the human umbilical vein endothelial cells (HUVEC) showed a dramatic decrease of tube formation ability. When the gel plugs used for the in vivo angiogenesis in the above section were stained with H&E, we observed that the numbers of apoptotic cells in the ADAMTS9 stable transfectant were dramatically increased. The numbers of apoptotic cells were also increased when growing in the absence of serum. Conclusions: Taken together, these studies indicate that ADAMTS9 is an important candidate tumor suppressor gene in NPC, which might mediate its tumor suppressive effects through the anti-angiogenic and pro-apoptotic mechanisms. 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 3058.