Open AccessSubstrate stiffness regulated migration and invasion ability of adenoid cystic carcinoma cells via RhoA/ ROCK pathway
Author(s) -
Zhao Dan,
Li Qianshun,
Liu Mengting,
Ma Wenjuan,
Zhou Tengfei,
Xue Changyue,
Cai Xiaoxiao
Publication year - 2018
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12442
Subject(s) - rhoa , adenoid cystic carcinoma , matrix metalloproteinase , stiffness , substrate (aquarium) , extracellular matrix , cancer research , cell migration , rho associated protein kinase , chemistry , microbiology and biotechnology , cell , medicine , biology , materials science , carcinoma , pathology , signal transduction , biochemistry , ecology , composite material
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 ACC 2 cells were cultured on polydimethylsiloxane substrates ( PDMS ) with varying stiffness for investigating the effects of substrate stiffness on the activities of MMP s and TIMP s. The underlying mechanism was also explored. Results When ACC 2 cells were cultured on various stiffness of PDMS , the expressions of matrix metalloproteinases 2 ( MMP 2), MMP 9, MMP 14, R hoA, R ac1, Rho‐associated protein kinase 1 ( ROCK 1) and ROCK 2 were up‐regulated with increasing substrate stiffness, whereas that of tissue inhibitor of matrix metalloproteinase 1 ( TIMP 1), TIMP 2 and TIMP 4 were down‐regulated with increasing substrate stiffness. Conclusions Our results showed that substrate stiffness regulated the activities of MMP s and TIMP s and then modulate migratory and invasive ability of ACC 2 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.