The Regulation Mechanism Of CXCR4 Receptor Response Axis For Migration And Invasion Of Thyroid Papillary Cancer Cell Line

Backgrounds and Objective:The incidence of thyroid cancer has increased year by year,including papillary carcinoma,follicular carcinoma,undifferentiated carcinoma and medullary carcinoma.Well-differentiated thyroid cancer accounts for more than 90%,but 20%-90% of patients with papillary thyroid carcinoma in the first diagnosed has occurred limited metastasis of lymph node,which seriously affect prognosis[ 3 ].Therefore,investigation of potential molecular mechanisms of thyroid cancer with metastasis is significant for finding new therapeutic targets.Stromal cell-derived factor-1 is a main member of chemokine protein family,CXCR4 is one of the major receptors of SDF-1,CXCR4 receptor response axis(CRRA)plays an important role in the generation and metastasis of tumors.CXCR4 is not expressed in normal thyroid cells and most well-differentiated thyroid tumor cells,but is highly expressed in thyroid cancer cells[6,7].In addition,overexpression of CXCR4 enhances SDF-1-induced cell invasion,but has no effect on cell proliferation.The aim of this study was to investigate the role and molecular mechanism of CRRA in cell mode of thyroid papillary cancer cell line.Material And Methods:1Material:82 cases of papillary thyroid carcinoma tissues were surgical resection specimens from 12/2014 to 5/2016 in CJUH of Jilin University;B-CPAP was purchased from Shanghai Zhong Qiao Xin Zhou biotechnology company.2Method:(1)The expression levels of CXCR4 in Papillary thyroid carcinoma tumors were detected.(2)The CXCR4 gene CDS region was designed and synthesized to construct a CXCR4 overexpressed plasmid.After 48 hours,detect the expression of CXCR4.(3)After CRRA treated,the ability of cell migration,invasion was detected.(4)After CRRA treated,the expression levels of E-cadherin,N-cadherin,Vimentin,NF-?B,p65,p-I?B and nucleus NF-?B were evaluated.(5)After CRRA,BAY11-7028(BAY)treated.Expression of NF-?B,p65,p-I?B and nucleus NF-?B were detected.Then ability of cell migration,invasion was detected.Results:(1)The expression level of CXCR4 in papillary thyroid carinoma tumors was high.(2)The expression of CXCR4 was significantly upregulated in B-CPAP-CXCR4 cells.(3)The ability of migration and invasion was increased with CRRA.(4)After CRRA treated,E-cadherin was significantly decreased,and N-cadherin and Vimentin were significantly increased,promote the EMT process.(5)CRRA can significantly increase the expression of NF-?B p65 in the nucleus,reduce the expression of NF-?B p65 in the cytoplasm,decrease the expression of P-I?B in the cell,active the signal pathway of NF-?B.(6)when BAY was treated into cells,NF-?B signaling pathway was inhibited.And EMT was inhibited.cell migration and cell invasion was inhibited.Conclusions:(1)CXCR4 receptor response axis can enhance the signal transduction of NF-?B pathway,promote the EMT process of thyroid papillary cancer cell,and enhance the migration and invasion of thyroid papillary cancer cell.(2)NF-?B pathway inhibitor BAY can weaken the promoting effect of CXCR4 receptor response axis on EMT process in thyroid papillary cancer cell, reduce the promote effect of CXCR4 receptor response axis on migration and invasionin in thyroid papillary cancer cell.NF-?B pathway may be a potential therapeutic target to inhibit the migration and invasion of thyroid papillary cancer cell.