Overexpression Cathepsin D Contributes to Perineural Invasion of Salivary Adenoid Cystic Carcinoma

Objective: Cathepsin D (CTSD) is a pivotal orchestrator in the occurrence and development of tumors. Recently, CTSD was detected in salivary adenoid cystic carcinoma (SACC). However, its functional role in perineural invasion (PNI) of SACC remained elusive. We conducted the present study to detect t...

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Main Authors: Mei Zhang, Jia-shun Wu, Xiao Yang, Xin Pang, Li Li, Sha-sha Wang, Jing-biao Wu, Ya-jie Tang, Xin-hua Liang, Min Zheng, Ya-ling Tang
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-10-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2018.00492/full
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author Mei Zhang
Mei Zhang
Mei Zhang
Jia-shun Wu
Jia-shun Wu
Jia-shun Wu
Xiao Yang
Xiao Yang
Xiao Yang
Xin Pang
Xin Pang
Xin Pang
Li Li
Sha-sha Wang
Sha-sha Wang
Sha-sha Wang
Jing-biao Wu
Jing-biao Wu
Jing-biao Wu
Ya-jie Tang
Xin-hua Liang
Xin-hua Liang
Xin-hua Liang
Min Zheng
Ya-ling Tang
Ya-ling Tang
Ya-ling Tang
author_facet Mei Zhang
Mei Zhang
Mei Zhang
Jia-shun Wu
Jia-shun Wu
Jia-shun Wu
Xiao Yang
Xiao Yang
Xiao Yang
Xin Pang
Xin Pang
Xin Pang
Li Li
Sha-sha Wang
Sha-sha Wang
Sha-sha Wang
Jing-biao Wu
Jing-biao Wu
Jing-biao Wu
Ya-jie Tang
Xin-hua Liang
Xin-hua Liang
Xin-hua Liang
Min Zheng
Ya-ling Tang
Ya-ling Tang
Ya-ling Tang
author_sort Mei Zhang
collection DOAJ
description Objective: Cathepsin D (CTSD) is a pivotal orchestrator in the occurrence and development of tumors. Recently, CTSD was detected in salivary adenoid cystic carcinoma (SACC). However, its functional role in perineural invasion (PNI) of SACC remained elusive. We conducted the present study to detect the expression of CTSD in SACC, analyze the correlation between CTSD expression and prognosis of SACC patients and elucidate the role of CTSD in occurrence of PNI in SACC to lay the foundation for further studies.Methods: Immunohistochemical analysis was conducted to assess CTSD and Ki67 expression in 158 SACC samples and 20 normal salivary gland samples adjacent to carcinoma. Meanwhile, the correlation between CTSD and PNI of SACC specimens was analyzed using Wilcoxon test. QRT-PCR, immunofluorescence and western blot analysis were used to examine the levels of CTSD mRNA and protein in SACC-LM cell line. SiRNA-mediated CTSD silence was performed. Scratch wound healing assay, transwell invasion assay and DRG co-culture assay of PNI was used to detect the ability of migration, invasion and PNI. FITC-phalloidin was used to detect cytoskeletal organization.Results: Our data demonstrated that the positive expression of CTSD was observed in 74.1% (117/158) of SACC cases, and the expression of CTSD was significantly correlated with the PNI (p < 0.05). The ability of migration, invasion, and PNI could be inhibited significantly by siRNA-mediated CTSD silence (p < 0.01). Furthermore, siRNA-mediated CTSD silence inhibited cytoskeletal organization and pseudo foot formation in SACC-LM cells.Conclusion: Our results suggested that an association between PNI and expression of CTSD existed. CTSD may promote PNI of SACC accompanied by cytoskeletal organization and pseudo foot formation.
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spelling doaj.art-39719c72bea14acb8969d9adbc8f05282022-12-22T00:29:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2018-10-01810.3389/fonc.2018.00492407725Overexpression Cathepsin D Contributes to Perineural Invasion of Salivary Adenoid Cystic CarcinomaMei Zhang0Mei Zhang1Mei Zhang2Jia-shun Wu3Jia-shun Wu4Jia-shun Wu5Xiao Yang6Xiao Yang7Xiao Yang8Xin Pang9Xin Pang10Xin Pang11Li Li12Sha-sha Wang13Sha-sha Wang14Sha-sha Wang15Jing-biao Wu16Jing-biao Wu17Jing-biao Wu18Ya-jie Tang19Xin-hua Liang20Xin-hua Liang21Xin-hua Liang22Min Zheng23Ya-ling Tang24Ya-ling Tang25Ya-ling Tang26State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaNational Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaNational Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaNational Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaNational Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Stomatology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, ChinaState Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaNational Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaNational Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaKey Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, ChinaState Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaNational Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Stomatology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, ChinaState Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaNational Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaObjective: Cathepsin D (CTSD) is a pivotal orchestrator in the occurrence and development of tumors. Recently, CTSD was detected in salivary adenoid cystic carcinoma (SACC). However, its functional role in perineural invasion (PNI) of SACC remained elusive. We conducted the present study to detect the expression of CTSD in SACC, analyze the correlation between CTSD expression and prognosis of SACC patients and elucidate the role of CTSD in occurrence of PNI in SACC to lay the foundation for further studies.Methods: Immunohistochemical analysis was conducted to assess CTSD and Ki67 expression in 158 SACC samples and 20 normal salivary gland samples adjacent to carcinoma. Meanwhile, the correlation between CTSD and PNI of SACC specimens was analyzed using Wilcoxon test. QRT-PCR, immunofluorescence and western blot analysis were used to examine the levels of CTSD mRNA and protein in SACC-LM cell line. SiRNA-mediated CTSD silence was performed. Scratch wound healing assay, transwell invasion assay and DRG co-culture assay of PNI was used to detect the ability of migration, invasion and PNI. FITC-phalloidin was used to detect cytoskeletal organization.Results: Our data demonstrated that the positive expression of CTSD was observed in 74.1% (117/158) of SACC cases, and the expression of CTSD was significantly correlated with the PNI (p < 0.05). The ability of migration, invasion, and PNI could be inhibited significantly by siRNA-mediated CTSD silence (p < 0.01). Furthermore, siRNA-mediated CTSD silence inhibited cytoskeletal organization and pseudo foot formation in SACC-LM cells.Conclusion: Our results suggested that an association between PNI and expression of CTSD existed. CTSD may promote PNI of SACC accompanied by cytoskeletal organization and pseudo foot formation.https://www.frontiersin.org/article/10.3389/fonc.2018.00492/fullcathepsin D (CTSD)salivary adenoid cystic carcinoma (SACC)perineural invasion (PNI)invasion frontiercytoskeletal organization
spellingShingle Mei Zhang
Mei Zhang
Mei Zhang
Jia-shun Wu
Jia-shun Wu
Jia-shun Wu
Xiao Yang
Xiao Yang
Xiao Yang
Xin Pang
Xin Pang
Xin Pang
Li Li
Sha-sha Wang
Sha-sha Wang
Sha-sha Wang
Jing-biao Wu
Jing-biao Wu
Jing-biao Wu
Ya-jie Tang
Xin-hua Liang
Xin-hua Liang
Xin-hua Liang
Min Zheng
Ya-ling Tang
Ya-ling Tang
Ya-ling Tang
Overexpression Cathepsin D Contributes to Perineural Invasion of Salivary Adenoid Cystic Carcinoma
Frontiers in Oncology
cathepsin D (CTSD)
salivary adenoid cystic carcinoma (SACC)
perineural invasion (PNI)
invasion frontier
cytoskeletal organization
title Overexpression Cathepsin D Contributes to Perineural Invasion of Salivary Adenoid Cystic Carcinoma
title_full Overexpression Cathepsin D Contributes to Perineural Invasion of Salivary Adenoid Cystic Carcinoma
title_fullStr Overexpression Cathepsin D Contributes to Perineural Invasion of Salivary Adenoid Cystic Carcinoma
title_full_unstemmed Overexpression Cathepsin D Contributes to Perineural Invasion of Salivary Adenoid Cystic Carcinoma
title_short Overexpression Cathepsin D Contributes to Perineural Invasion of Salivary Adenoid Cystic Carcinoma
title_sort overexpression cathepsin d contributes to perineural invasion of salivary adenoid cystic carcinoma
topic cathepsin D (CTSD)
salivary adenoid cystic carcinoma (SACC)
perineural invasion (PNI)
invasion frontier
cytoskeletal organization
url https://www.frontiersin.org/article/10.3389/fonc.2018.00492/full
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