The Role And Mechanism Of Extracellular Matrix Protein CCBE1 In Tumor

Tumor,especially malignant,has caused tremendous damage to human health as one of the most serious public health problems.Extracellular matrix(ECM),as important components of tumor micro-environment,plays vital roles in the process of tumor development and has close relationship with tumor progression and prognosis.In previous studies,we have analyzed several databases of gene expression profiles and found the CCBE1(Collagen and calcium-binding EGF domain)expression level down-regulated in breast cancer,gastric cancer,liver cancer and ovarian cancer,while up-regulation of CCBE1 expression level has been found in high-risk gastrointestinal stromal tumor(GIST).We have mainly researched the function of CCBE1 in the development and progression of liver cancer and GIST,as well as its molecular mechanism.In liver cancer,we have found that the CCBE1 expression level is associated with tumor size,tumor capsule,vascular invasion and TNM stage,and positively correlated with prognosis.It has been proved that the methylation level in liver cancer tissues and cells is obviously higher than the adjacent tumor tissues and cells.In vitro and vivo experiments,we have found that the up-regulation of CCBE1 expression can evidently inhibit the proliferation,metastasis,oxygen consumption rate of liver cancer cells.Furthermore,to clarify the mechanism of CCBE1 in liver cancer,we have assumed the interaction between CCBE1 proteins with NOTCH receptors,which needs further exploration.In gastrointestinal stromal tumor(GIST),we have found the CCBE1 expression level negatively correlated with prognosis.Through the analysis of gene expression profile chips,it has been found that the CCBE1 expression is associated with tumor size,NIH danger grade and recurrence.Especially,the CCBE1 protein significantly exists in vascular walls.In vitro experiments,the CCBE1 expression level of GIST cells significantly increases after treatment with imatinib;recombinant CCBE1(rCCBE1)protein can partially reduce the anti-tumor effects of imatinib on GIST-T1 and enhance angiogenesis.Above all,in this study,we reveal the multiple biological function of CCBE1 in liver cancer and GIST,and speculate that the CCBE1 can become a novel prognostic indicator and treatment target.