Substrate stiffness regulated migration and invasion ability of adenoid cystic carcinoma cells via RhoA/ROCK pathway

• Published in: Cell proliferation 2018-06, Vol.51 (3), p.e12442-n/a
• Main Authors: Zhao, Dan, Li, Qianshun, Liu, Mengting, Ma, Wenjuan, Zhou, Tengfei, Xue, Changyue, Cai, Xiaoxiao
• Format: Article
• Language: English
• Subjects: Adenoid; Carcinoma, Adenoid Cystic - metabolism; Carcinoma, Adenoid Cystic - pathology; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Shape; Culture Media - chemistry; Dimethylpolysiloxanes - chemistry; Extracellular Matrix - metabolism; Gelatinase A; Gelatinase B; Humans; Invasiveness; Kinases; Matrix metalloproteinase; Matrix metalloproteinases; Matrix Metalloproteinases - metabolism; Medical prognosis; Metalloproteinase; Neoplasm Invasiveness; Original; Polydimethylsiloxane; Protein kinase; Proteins; Rac1 protein; Rho-associated kinase; rho-Associated Kinases - metabolism; rhoA GTP-Binding Protein - metabolism; RhoA protein; Rocks; Salivary gland; Signal Transduction; Silicone resins; Solid tumors; Stiffness; Substrate inhibition; Substrates; Tissue inhibitor of metalloproteinase 1; Tissue inhibitor of metalloproteinase 2; Tissue inhibitor of metalloproteinase 4; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Tumors
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/cpr.12442

Objectives Human salivary adenoid cystic carcinoma (SACC) is one of the most common malignant tumours of the salivary gland and has strong migratory and invasive ability, which often lead to poor prognosis and lower survival rate. Tumour tissue tends to stiffen during solid tumour progression. This study aimed to investigate the influence of various substrate stiffness on the migration and invasion of SACC. Methods Salivary adenoid cystic carcinoma cell line ACC2 cells were cultured on polydimethylsiloxane substrates (PDMS) with varying stiffness for investigating the effects of substrate stiffness on the activities of MMPs and TIMPs. The underlying mechanism was also explored. Results When ACC2 cells were cultured on various stiffness of PDMS, the expressions of matrix metalloproteinases 2 (MMP2), MMP9, MMP14, RhoA, Rac1, Rho‐associated protein kinase 1 (ROCK1) and ROCK2 were up‐regulated with increasing substrate stiffness, whereas that of tissue inhibitor of matrix metalloproteinase 1 (TIMP1), TIMP2 and TIMP4 were down‐regulated with increasing substrate stiffness. Conclusions Our results showed that substrate stiffness regulated the activities of MMPs and TIMPs and then modulate migratory and invasive ability of ACC2 cells via RhoA/ROCK pathway. This work indicate that matrix stiffness played an important role in progression of SACC, which not only can help understand the strong invasive ability of SACC, but also suggested that therapeutically targeting matrix stiffness may help reduce migration and invasion of SACC and improve effective therapies.