Dataset Information

Heterogeneous Responses to Mechanical Force of Prostate Cancer Cells Inducing Different Metastasis Patterns.

ABSTRACT: The physical cues in the extracellular environment play important roles in cancer cell metastasis. However, how metastatic cancer cells respond to the diverse mechanical environments of metastatic sites is not fully understood. Here, substrates with different mechanical properties are prepared to simulate the extracellular mechanical environment of various human tissues. The prostate cancer (PC) cells derived from different cancer metastasis sites show heterogeneity in mechanical response. This heterogeneity mediates two distinct metastasis patterns. High stiffness promotes individual cell migration and proliferation by inducing Yes-associated protein and tafazzin (YAP/TAZ) nuclear localization in bone metastasis-derived cells, whereas low stiffness promotes cell migration and proliferation by inducing lymphatic metastasis-derived cells to form clusters characterized by high expression of CD44. The different metastasis patterns induced by the mechanical properties of the extracellular environment are crucial in the development of PC.

SUBMITTER: Liu Z

PROVIDER: S-EPMC7404165 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Heterogeneous Responses to Mechanical Force of Prostate Cancer Cells Inducing Different Metastasis Patterns.

Liu Zhixiao Z Wang Liujun L Xu Huan H Du Qiqige Q Li Li L Wang Ling L Zhang En Song ES Chen Guosong G Wang Yue Y

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200617 15

The physical cues in the extracellular environment play important roles in cancer cell metastasis. However, how metastatic cancer cells respond to the diverse mechanical environments of metastatic sites is not fully understood. Here, substrates with different mechanical properties are prepared to simulate the extracellular mechanical environment of various human tissues. The prostate cancer (PC) cells derived from different cancer metastasis sites show heterogeneity in mechanical response. This ...[more]

PMID: 32775149

Similar Datasets

Project description:Cancer deaths are primarily caused by metastases, not by the parent tumor. During metastasis, malignant cells detach from the parent tumor, and spread through the circulatory system to invade new tissues and organs. The physical-chemical mechanisms and parameters within the cellular microenvironment that initiate the onset of metastasis, however, are not understood. Here we show that human colon carcinoma (HCT-8) cells can exhibit a dissociative, metastasis-like phenotype (MLP) in vitro when cultured on substrates with appropriate mechanical stiffness. This rather remarkable phenotype is observed when HCT-8 cells are cultured on gels with intermediate-stiffness (physiologically relevant 21-47 kPa), but not on very soft (1 kPa) and very stiff (3.6 GPa) substrates. The cell-cell adhesion molecule E-Cadherin, a metastasis hallmark, decreases 4.73 ± 1.43 times on cell membranes in concert with disassociation. Both specific and nonspecific cell adhesion decrease once the cells have disassociated. After reculturing the disassociated cells on fresh substrates, they retain the disassociated phenotype regardless of substrate stiffness. Inducing E-Cadherin overexpression in MLP cells only partially reverses the MLP phenotype in a minority population of the dissociated cells. This important experiment reveals that E-Cadherin does not play a significant role in the upstream regulation of the mechanosensing cascade. Our results indicate, during culture on the appropriate mechanical microenvironment, HCT-8 cells undergo a stable cell-state transition with increased in vitro metastasis-like characteristics as compared to parent cells grown on standard, very stiff tissue culture dishes. Nuclear staining reveals that a large nuclear deformation (major/minor axis ratio, 2:5) occurs in HCT-8 cells when cells are cultured on polystyrene substrates, but it is markedly reduced (ratio, 1:3) in cells grown on 21 kPa substrates, suggesting the cells are experiencing different intracellular forces when grown on stiff as compared to soft substrates. Furthermore, MLP can be inhibited by blebbistatin, which inactivates myosin II activity and relaxes intracellular forces. This novel finding suggests that the onset of metastasis may, in part, be linked to the intracellular forces and the mechanical microenvironment of the tumor.

Dataset Information

Heterogeneous Responses to Mechanical Force of Prostate Cancer Cells Inducing Different Metastasis Patterns.

Publications

Heterogeneous Responses to Mechanical Force of Prostate Cancer Cells Inducing Different Metastasis Patterns.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets