Cathepsin B defines leader cells during the collective invasion of salivary adenoid cystic carcinoma

Wu,Jia‑Shun; Li,Zhu‑Feng; Wang,Hao‑Fan; Yu,Xiang‑Hua; Pang,Xin; Wu,Jing‑Biao; Wang,Sha‑Sha; Zhang,Mei; Yang,Xiao; Cao,Ming‑Xin; Tang,Ya‑Jie; Liang,Xin‑Hua; Zheng,Min; Tang,Ya‑Ling

doi:10.3892/ijo.2019.4722

Cathepsin B defines leader cells during the collective invasion of salivary adenoid cystic carcinoma

Authors:
- Jia‑Shun Wu
- Zhu‑Feng Li
- Hao‑Fan Wang
- Xiang‑Hua Yu
- Xin Pang
- Jing‑Biao Wu
- Sha‑Sha Wang
- Mei Zhang
- Xiao Yang
- Ming‑Xin Cao
- Ya‑Jie Tang
- Xin‑Hua Liang
- Min Zheng
- Ya‑Ling Tang
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Affiliations: State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology (Sichuan University), Chengdu, Sichuan 610041, P.R. China, Key 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, Hubei 430068, P.R. China, Department of Stomatology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, Zhejiang 316021, P.R. China
Published online on: February 22, 2019 https://doi.org/10.3892/ijo.2019.4722
Pages: 1233-1244
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cathepsin B (CTSB) has been reported to be involved in cancer metastasis by altering extracellular matrix (ECM) remodeling and facilitating invasion. However, the contribution of CTSB to collective cell invasion in salivary adenoid cystic carcinoma (SACC) and the underlying mechanisms remain unclear. The present study demonstrated that collective cell invasion is commonly observed in SACC without a complete epithelial‑mesenchymal transition signature. CTSB was found to be overexpressed in the invasive front of SACC compared to the tumor center, and was associated with a poor prognosis of patients with SACC. Subsequently, a 3D spheroid invasion assay was established in order to recapitulate the collective cell invasion of SACC and the results revealed that CTSB was only expressed in leader cells. The knockdown of CTSB by siRNA inhibited the migration and invasion of SACC‑83 cells and impaired the formation of leader cells. CTSB knockdown also disrupted cytoskeletal organization, altered cell morphology and inhibited ECM remodeling by downregulating matrix metalloproteinase‑9, focal adhesion kinase and Rho/ROCK function. Therefore, the present study provides evidence that CTSB may define leader cells in SACC and is required for collective cell invasion as a potential key regulator of ECM remodeling.

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