Areca nut use is the major cause of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis （OSF） in Eastern and Southern Asians. Areca nut contains a high level of free copper ions. Lysyl oxidase (LOX) is a copper-activated enzyme critical for extracellular matrix organization. Contradictory evidence has been put forward to suggest that LOX may be either an oncogenic or a suppressive element. In previous study, both normal human oral keratinocyte （NHOK） and OECM-1, an oral cancer cell line, LOX mRNA expression were induced by areca nut extract （ANE） treatment after 24 h. Up-regulation of LOX mRNA and LOX protein expression in OSCCs relative to adjacent oral mucosa were found. Knock-down of LOX induced cellular migration and invasion but it reduced the anchorage-independent growth and xenographic tumorigenesis of OSCC cells. LOX exerts oncogenic roles in areca-associated OSCC. In previous study, silence LOX expression of SAS inhibited xenographic tumorigenesis ability, and enhanced when LOX overexpressed. However, the SAS and OECM-1 proliferation rate did not affect by LOX abnormal expression. Beside LOX can affect tumor metastasis, LOX expression also affect primary tumor growth. It is interesting overexpressed LOX how to help primary tumor growth. Angiogenesis is the one of major factors to determine tumor growth. So LOX might have some relations between angiogenesis. There are three aims in the study：（1） set up LOX overexpression and silence OSCC cell line, and confirm whether LOX affect cell growth.（2） whether LOX direct and indirect interaction with angiogenesis in vitro. (3) in vivo model test whether LOX affect vasculogenesis and angiogenesis. The overall achievements of this grant will enhance our understanding on LOX whether a positive factor for OSCC angiogenesis. The findings may be beneficial for the interception of oral carcinogenesis in further preclinical study
