Expression Of AXL And PROS1 In Papillary Thyroid Carcinoma

Objective: To explore the transcriptional expression of TAM signaling pathwayrelated ligand Pros1 and receptor AXL in human papillary thyroid carcinoma(PTC),analyze the expression of AXL in human PTC and normal thyroid tissues and the effect of blocking PROS1-AXL pathway on PTC cells,provide exprerimental data for elucidating the role of TAM pathway in the pathogenesis of PTC.Methods: 1)culturing human PTC and human normal thyroid cells from general surgery laboratory of General Hospital of Tianjin Medical University.Two of the them are TPC-1 and B-CPAP respectively,which are both TPC cell lines taking as experimental groups,another one is Nthy-Ori 3-1,which is the only strain of normal thyroid cells taking as control group.cells were harvested and mRNA were extracted each of them,PROS1 expression level were acquired by RT-qPCR consequently.2)Immunohistochemistry was used to assess AXL positivity of 40 PTC inpatients’ biopsy-confirmed cancer specimen along with its adjacent normal thyroid tissue,24 of them were PTMC.Collect all the pathological and clinical data to compare the differency among the various AXL positity.3)Blocked the PROS1-AXL downstream pathway of B-CPAP cell lines by specific AXL antagonist R428,non-R428 treated BCPAP cell as control group,then analyzed the results by CCK-8、Scratching methods to evaluate cell proliferation and migration ability change.Results: 1)there were different mRNA expression of both PROS1 and AXL in TPC-1,B-CPAP,and Nthy-Ori 3-1 cell lines,the mRNA level of TPC-1 and B-CPAP are significantly higher than that in Nthy-Ori 3-1 and the B-CPAP’s result are overwhelmingly explained it(p<0.05).2)AXL in human PTC specimen are markedly expressed,but not in adjacent normal thyroid tissues(p<0.05).3)After been treated by AXL antagonist R428 with different concentration level,TPC-1,B-CPAP cells showed lower proliferative ability than control group which been not treated by R428.Moreover,R428-treated cell lins showed different level of declining in cell proliferation associated with drug concentration range of 0.5μM to 4μM and showed dose-dependent effect(p < 0.01).Compared with the control group,R428 also produced different degrees of inhibitory effects on the migration of PTC cell lines in the drug concentration range of 0.5 μM to 2μM(p<0.01).Conclusions: comparing with the human normal thyroid cells,PROS1 and its downstream receptor AXL are both highly expressed in human PTC cell lines.AXL is highly expressed in human PTC specimens ranther than normal thyroid tissues.After administering the AXL inhibitor R428.It shows that blocking the PROS1-AXLmediated TAM signaling pathway can inhibit the proliferation and migration of human PTC cells,and preliminary revealed its role in the occurrence and progress of human PTC.