Inhibition of matrix stiffness relating integrin β1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts

Abstract Background Cancer development is strictly correlated to composition and physical properties of the extracellular matrix. Particularly, a higher matrix stiffness has been demonstrated to promote tumor sustained growth. Our purpose was to explore the role of matrix stiffness in liver cancer d...

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Autores principales:	Changsong Wang, Xiaozhong Jiang, Bin Huang, Wenhao Zhou, Xiao Cui, Chenghong Zheng, Fenghao Liu, Jieling Bi, Yi Zhang, Hong Luo, Lin Yuan, Jianyong Yang, Yu Yu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Matrix stiffness Integrin β1 ERK1/2 Hepatocellular cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0c5dd03a69ec40ca9436e0452e5fc05b
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spelling	oai:doaj.org-article:0c5dd03a69ec40ca9436e0452e5fc05b2021-11-28T12:27:47ZInhibition of matrix stiffness relating integrin β1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts10.1186/s12885-021-08982-31471-2407https://doaj.org/article/0c5dd03a69ec40ca9436e0452e5fc05b2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08982-3https://doaj.org/toc/1471-2407Abstract Background Cancer development is strictly correlated to composition and physical properties of the extracellular matrix. Particularly, a higher matrix stiffness has been demonstrated to promote tumor sustained growth. Our purpose was to explore the role of matrix stiffness in liver cancer development. Methods The matrix stiffness of tumor tissues was determined by atomic force microscopy (AFM) analysis. In vitro, we used a tunable Polyacrylamide (PA) hydrogels culture system for liver cancer cells culture. The expression level of integrin β1, phosphorylated FAK, ERK1/2, and NF-κB in SMMC-7721 cells was measured by western blotting analysis. We performed MTT, colony formation and transwell assay to examine the tumorigenic and metastatic potential of SMMC-7721 cells cultured on the tunable PA hydrogels. SMMC-7721 cancer xenografts were established to explore the anticancer effects of integrin inhibitors. Results Our study provided evidence that liver tumor tissues from metastatic patients possessed a higher matrix stiffness, when compared to the non-metastatic group. Liver cancer cells cultured on high stiffness PA hydrogels displayed enhanced tumorigenic potential and migrative properties. Mechanistically, activation of integrin β1/FAK/ ERK1/2/NF-κB signaling pathway was observed in SMMC-7721 cells cultured on high stiffness PA hydrogels. Inhibition of ERK1/2, FAK, and NF-κB signaling suppressed the pro-tumor effects induced by matrix stiffness. Combination of chemotherapy and integrin β1 inhibitor suppressed the tumor growth and prolonged survival time in hepatocellular cancer xenografts. Conclusion A higher matrix stiffness equipped tumor cells with enhanced stemness and proliferative characteristics, which was dependent on the activation of integrin β1/FAK/ERK1/2/NF-κB signaling pathway. Blockade of integrin signals efficiently improved the outcome of chemotherapy, which described an innovative approach for liver cancer treatment.Changsong WangXiaozhong JiangBin HuangWenhao ZhouXiao CuiChenghong ZhengFenghao LiuJieling BiYi ZhangHong LuoLin YuanJianyong YangYu YuBMCarticleMatrix stiffnessIntegrin β1ERK1/2Hepatocellular cancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Matrix stiffness Integrin β1 ERK1/2 Hepatocellular cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Matrix stiffness Integrin β1 ERK1/2 Hepatocellular cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Changsong Wang Xiaozhong Jiang Bin Huang Wenhao Zhou Xiao Cui Chenghong Zheng Fenghao Liu Jieling Bi Yi Zhang Hong Luo Lin Yuan Jianyong Yang Yu Yu Inhibition of matrix stiffness relating integrin β1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts
description	Abstract Background Cancer development is strictly correlated to composition and physical properties of the extracellular matrix. Particularly, a higher matrix stiffness has been demonstrated to promote tumor sustained growth. Our purpose was to explore the role of matrix stiffness in liver cancer development. Methods The matrix stiffness of tumor tissues was determined by atomic force microscopy (AFM) analysis. In vitro, we used a tunable Polyacrylamide (PA) hydrogels culture system for liver cancer cells culture. The expression level of integrin β1, phosphorylated FAK, ERK1/2, and NF-κB in SMMC-7721 cells was measured by western blotting analysis. We performed MTT, colony formation and transwell assay to examine the tumorigenic and metastatic potential of SMMC-7721 cells cultured on the tunable PA hydrogels. SMMC-7721 cancer xenografts were established to explore the anticancer effects of integrin inhibitors. Results Our study provided evidence that liver tumor tissues from metastatic patients possessed a higher matrix stiffness, when compared to the non-metastatic group. Liver cancer cells cultured on high stiffness PA hydrogels displayed enhanced tumorigenic potential and migrative properties. Mechanistically, activation of integrin β1/FAK/ ERK1/2/NF-κB signaling pathway was observed in SMMC-7721 cells cultured on high stiffness PA hydrogels. Inhibition of ERK1/2, FAK, and NF-κB signaling suppressed the pro-tumor effects induced by matrix stiffness. Combination of chemotherapy and integrin β1 inhibitor suppressed the tumor growth and prolonged survival time in hepatocellular cancer xenografts. Conclusion A higher matrix stiffness equipped tumor cells with enhanced stemness and proliferative characteristics, which was dependent on the activation of integrin β1/FAK/ERK1/2/NF-κB signaling pathway. Blockade of integrin signals efficiently improved the outcome of chemotherapy, which described an innovative approach for liver cancer treatment.
format	article
author	Changsong Wang Xiaozhong Jiang Bin Huang Wenhao Zhou Xiao Cui Chenghong Zheng Fenghao Liu Jieling Bi Yi Zhang Hong Luo Lin Yuan Jianyong Yang Yu Yu
author_facet	Changsong Wang Xiaozhong Jiang Bin Huang Wenhao Zhou Xiao Cui Chenghong Zheng Fenghao Liu Jieling Bi Yi Zhang Hong Luo Lin Yuan Jianyong Yang Yu Yu
author_sort	Changsong Wang
title	Inhibition of matrix stiffness relating integrin β1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts
title_short	Inhibition of matrix stiffness relating integrin β1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts
title_full	Inhibition of matrix stiffness relating integrin β1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts
title_fullStr	Inhibition of matrix stiffness relating integrin β1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts
title_full_unstemmed	Inhibition of matrix stiffness relating integrin β1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts
title_sort	inhibition of matrix stiffness relating integrin β1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts
publisher	BMC
publishDate	2021
url	https://doaj.org/article/0c5dd03a69ec40ca9436e0452e5fc05b
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Inhibition of matrix stiffness relating integrin β1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts

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