Effect of extracellular matrix stiffness on tumor progression and treatment strategies
BACKGROUND:The extracellular matrix is a complex network structure,which not only builds physical support for tissue cells,but also plays an important regulatory role in cell survival,proliferation,and death.Abnormal changes in the biochemical and biomechanical properties of the extracellular matrix can significantly affect the proliferation,migration,immune evasion,and treatment resistance of tumor cells.Stiffness is an important mechanical property of the extracellular matrix,and abnormalities in matrix stiffness are closely related to tumor progression.OBJECTIVE:By reviewing the mechanism of extracellular matrix sclerosis,the impact of high stiffness matrix on tumor progression,and the latest research progress in the treatment of cancer based on reducing matrix stiffness,to deeply understand the mechanical properties of the extracellular matrix,improve the understanding of the complex mechanism of tumor progression,and provide new ideas and directions for tumor treatment.METHODS:"Extracellular matrix function,extracellular matrix stiffness,collagen deposition cross-linking,extracellular matrix stiffness therapy,immunotherapy"were used as the search terms in Chinese and English.Relevant literature published from January 2016 to June 2024 was searched in CNKI,PubMed,and WanFang databases,and 80 articles were finally included for review.RESULTS AND CONCLUSION:(1)Deposition and excessive cross-linking of collagen and elastin in the extracellular matrix leads to matrix remodeling,which in turn increases matrix stiffness.This sclerosis activates pro-cancer signaling pathways such as cyclin-D1,Rho/ROCK,p-PXN-Rac1-YAP,and STAT3/p-STAT3,promotes malignant behaviors such as cancer cell proliferation,metastasis,tumor microangiogenesis and immune escape,and accelerates tumor progression.(2)Reducing the deposition and cross-linking of matrix proteins can reduce matrix stiffness,which cannot only inhibit the activation of multiple cancer-promoting signaling pathways,but also enhance the penetration and delivery of drugs at tumor sites,which is a new strategy for cancer treatment.(3)At present,drugs based on matrix degradation to reduce tumor stiffness are under development,and a few drugs have entered the clinical trial stage,which are expected to provide a new powerful weapon for tumor treatment.
matrix stiffnesstumor cellsbiological behaviorcancer treatmentimmunotherapyextracellular matrixengineered tissue construction
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