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

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 epithelial­mesenchymal 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 SACC­83 cells and impaired the formation of leader cells. CTSB knockdown also disrupted cytoskeletal organization, altered cell morphology and inhibited ECM remodeling by downregulating matrix metalloproteinase­9, 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.