The Expression And Significance Of Slug And EMMPRIN And E-cadherin In Salivary Adenoid Cystic Carcinoma

Salivary adenoid cystic carcinoma(SACC) is one of the most prevalent malignant tumors in salivary epithelium. Perineural invasion and distant metastasis are the unique feathers of SACC, which is also the reason of poor long-term prognosis. Epithelial-mesenchymal transition(EMT) has played a key role during the invasion and metastasis of malignant oral tumors. The downregulation of E-cadherin is considered to be the iconic event of EMT. Slug, a member of zinc finger transcription factor family, expresses more in maligants than in normal tissues. It participates in the EMT regulation and is closely related to tumor invasion, metastasis and prognosis. EMMPRIN is a transmembrane glycoprotein which is widely expressed in human body. It has been proved that EMMPRIN can promote SACC invasion and metastasis via various pathways. To date as we know, the Slug, EMMPRIN and E-cadherin are closely related to the development of hepatocellular carcinoma, while their relationships in SACC have not been elucidated.Part one: Objectives: To figure out the relationships of the expression level of Slug, EMMPRIN and E-cadherin in clinical pathology in SACC. Methods: A total of 115 SACC samples were obtained from the Department of Oral and Maxillofacial Surgery, the Fourth Military Medical University. The Slug, EMMPRIN and E-cadherin expression level was checked by immunohistochemistry and compared with the related clinical pathology. Data was processed with Fisher test using SPSS 17.0. Results: Slug and EMMPRIN were strongly positive expressed with the rate of 76.5% and 69.6% respectively. E-cadherin was weakly positive expressed with the rate of 51.3%. Slug and EMMPRIN expression level was significant positive correlation with the pathological type, clinical stage, perineural invasion, relapse and distant metastasis of SACC(P<0.05). E-cadherin was significant negative correlation with the pathological type, clinical stage, perineural invasion and distant metastasis of SACC. Slug was significantly correlated with EMMPRIN(P<0.05). EMMPRIN was negatively significantly correlated with E-cadherin(P<0.05). Slug was negatively significantly correlated with E-cadherin(P<0.05). Conclusions: Slug, EMMPRIN and E-cadherin expression are significantly correlated with SACC pathological behaviors.Part two: Objectives: To reveal the roles of Slug, EMMPRIN and E-cadherin may play during perineural invasion of SACC and their interactions. Methods: Two plasmids(si-Slug, si-EMMPRIN) were established and transfected into SACC-83 cell line. G1: blank control; G2: si-Slug; G3: si-EMMPRIN; G4: si-Slug and si-EMMPRIN( raito 1:1). The RT-PCR, western blot, morphological observation, scratch test, invasion assay and migration assays were performed after transfection. Results: Silencing Slug or EMMPRIN leads to the suppression of the movement ability and perineural invasion ability of SACC-83. Conclusions: Slug upregulates EMMPRIN to suppress E-cadherin expression in EMT process and plays an important role during the perineural invasion in SACC. Slug and EMMPRIN may be developed as diagnostic markers of SACC and serve as targets for tumor therapy.