精准医学杂志 (Jun 2024)

Regulatory effect of extracellular matrix stiffness on the plasticity of human prostate cancer cells

  • ZHENG Yu, MA Lei, LI Ruizhi, MU Jie, LI Jing, WANG Dong, ZHU Hai

DOI
https://doi.org/10.13362/j.jpmed.202403008
Journal volume & issue
Vol. 39, no. 3
pp. 222 – 225

Abstract

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Objective To investigate the regulatory effect of extracellular matrix (ECM) stiffness on the plasticity of human prostate cancer cells (LNCaP). Methods Human LNCaP cells were cultured in ECM culture dishes with four types of stiffness (i.e., Young’s modulus of 3 GPa [group A], 20 kPa [group B], 6 kPa [group C], and 1 kPa [group D]) for one week. The morphology of cells on substrates of different stiffness values was observed for each group using bright-field microscopy and fluorescence microscopy. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression levels of luminal cell marker genes (AR, CK8, CK18, and PSA), basal cell marker genes (CK5 and P63), and proliferative genes (KI67 and PCNA) in each group. Results Bright-field microscopy and fluorescence microscopy showed that human LNCaP cells in group A exhibited typically spread epithelial cell morphology, whereas the cells in groups B to D showed the state of agglomerated small cell sheets, and the cells in group D formed a three-dimensional organ-like structure. RT-qPCR results showed that there were no significant differences between the four groups in the expression levels of KI67 and P63 genes in human LNCaP cells (P>0.05). The expression level of PCNA gene in group B was significantly higher than that in groups A and C (F=34.96,t=8.39,6.37,P<0.05). The expression level of CK5 gene in group B was significantly higher than that in the other three groups (F=29.35,t=4.46-6.73,P<0.05). The expression levels of AR, CK8, CK18, and PSA genes in group D were significantly higher than those in the other three groups (F=13.66-56.43, t=3.03-11.51,P<0.05). Conclusion ECM environment with a lower stiffness value (Young’s modulus of 1 kPa) can better maintain the luminal cell characteristics of human LNCaP cells, whereas ECM with a higher stiffness value (Young’s modulus of 20 kPa) causes human LNCaP cells to exhibit an intermediate state cellular phenotype, which may be one of the factors leading to the development of prostate cancer.

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