The Function And Mechanism Study Of ADAMTS-18 On Tumor Initiation,development And Metastasis

Backgrounds:A Disintegrin-like And Metalloproteinase with Thrombospondin type 1 motif-18 (ADAMTS-18) gene has been found to be epigenetically silenced in multiple carcinomas. The deletion of chromosome 16q, which contains ADAMTS-18 gene, is associated with the prognosis and survival of breast carcinomas. Futhermore, ADAMTS-18 mutations increase melanoma migration in vitro and metastasis in vivo. Putting it all together, these investigations suggest ADAMTS-18 is a novel tumor suppressor gene.Methods:We successfully constructed Adamts-18 knockout (KO) mice, and observed the phenotypic differences of KO and wide-type (WT) mice in two tumor models to analyze the functions of Adamts-18 gene in the process of tumor initiation, development and metastasis.Results:The rate of knockout, heterozygote, and wild-type from heterozygote crossing is nearly 1:2:1. We don’t find embryonic lethality and spontaneous tumorgenesis. All the experimental data of KO and WT mice had no statistical differences in mouse colon cancer model induced by azoxymethabe (AOM). In subcutaneous melanoma model, we found that the both tumor volume and final tumor weight in KO mice was significantly larger than WT mice.Conclusion:Adamts-18 gene plays a role in the progression of melanoma, but more tumor models are needed to confirm its function in tumor development.