Details

Autor(en) / Beteiligte

• Zhang, Rui
• Ma, Min
• Dong, Gang
• Yao, Rong‐Rong
• Li, Jing‐Huan
• Zheng, Qiong‐Dan
• Dong, Yin‐Ying
• Ma, Hui
• Gao, Dong‐Mei
• Cui, Jie‐Feng
• Ren, Zheng‐Gang
• Chen, Rong‐Xin

Titel

Increased matrix stiffness promotes tumor progression of residual hepatocellular carcinoma after insufficient heat treatment

Ist Teil von

• Cancer science, 2017-09, Vol.108 (9), p.1778-1786

Ort / Verlag

England: John Wiley & Sons, Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Aggravated behaviors of hepatocellular carcinoma (HCC) will occur after inadequate thermal ablation. However, its underlying mechanisms are not fully understood. Here, we assessed whether the increased matrix stiffness after thermal ablation could promote the progression of residual HCC. Heat‐treated residual HCC cells were cultured on tailorable 3D gel with different matrix stiffness, simulating the changed physical environment after thermal ablation, and then the mechanical alterations of matrix stiffness on cell phenotypes were explored. Increased stiffness was found to significantly promote the proliferation of the heat‐treated residual HCC cells when the cells were cultured on stiffer versus soft supports, which was associated with stiffness‐dependent regulation of ERK phosphorylation. Heat‐exposed HCC cells cultured on stiffer supports showed enhanced motility. More importantly, vitamin K1 reduced stiffness‐dependent residual HCC cell proliferation by inhibiting ERK phosphorylation and suppressed the in vivo tumor growth, which was further enhanced by combining with sorafenib. Increased matrix stiffness promotes the progression of heat‐treated residual HCC cells, proposing a new mechanism of an altered biomechanical environment after thermal ablation accelerates HCC development. Vitamin K1 plus sorafenib can reverse this protumor effect. Increased matrix stiffness after thermal ablation accelerates the progression of heat‐exposed residual HCC cells. Vitamin K1 and sorafenib disrupt the stiffness‐induced ERK activation to reverse the pro‐tumor effect as the potential therapeutic drugs. This new finding will help design strategy to treat the local tumor progression and prevent its rapid progression after RFA in the treatment of medium or large HCC.