PUBLICATION
Efficient extravasation of tumor-repopulating cells depends on cell deformability
- Authors
- Chen, J., Zhou, W., Jia, Q., Chen, J., Zhang, S., Yao, W., Wei, F., Zhang, Y., Yang, F., Huang, W., Zhang, Y., Zhang, H., Zhang, Y., Huang, B., Zhang, Z., Jia, H., Wang, N.
- ID
- ZDB-PUB-160121-6
- Date
- 2016
- Source
- Scientific Reports 6: 19304 (Journal)
- Registered Authors
- Huang, Wei, Jia, Haibo
- Keywords
- Cancer microenvironment, Cancer stem cells, Stress fibres
- MeSH Terms
-
- Actins/chemistry
- Actins/metabolism
- Animals
- Cell Line, Tumor
- Cell Proliferation
- Disease Models, Animal
- Disease Progression
- Gene Expression Regulation, Neoplastic
- Gene Silencing
- Melanoma, Experimental
- Mice
- Neoplasm Metastasis
- Neoplasms/genetics
- Neoplasms/metabolism*
- Neoplasms/pathology*
- Neoplastic Stem Cells/metabolism*
- SOXB1 Transcription Factors/genetics
- SOXB1 Transcription Factors/metabolism
- Zebrafish
- cdc42 GTP-Binding Protein/genetics
- cdc42 GTP-Binding Protein/metabolism
- PubMed
- 26787224 Full text @ Sci. Rep.
Citation
Chen, J., Zhou, W., Jia, Q., Chen, J., Zhang, S., Yao, W., Wei, F., Zhang, Y., Yang, F., Huang, W., Zhang, Y., Zhang, H., Zhang, Y., Huang, B., Zhang, Z., Jia, H., Wang, N. (2016) Efficient extravasation of tumor-repopulating cells depends on cell deformability. Scientific Reports. 6:19304.
Abstract
Cancer metastasis is the most deadly stage in cancer progression. Despite significant efforts over the past decades, it remains elusive why only a very small fraction of cancer cells is able to generate micrometastasis and metastatic colonization. Recently we have shown that tumor-repopulating cells (TRCs), a highly tumorigenic subpopulation of mouse melanoma cells, can be selected by being cultured and grown in 3D soft fibrin gels. Here we show that when injected into the yolk of a 2 day-post-fertilization (dpf) embryo of Tg (fli1:EGFP or kdrl:mCherry) zebrafish, TRCs are much more efficient in surviving and growing at various secondary sites to generate micrometastasis and metastatic colonization than control melanoma cells that are grown on rigid plastic. The metastasis of TRCs is dependent on the presence of Sox2, a self-renewal gene, and silencing Sox2 leads to the inhibition of TRC metastasis. High-resolution of 3D confocal images of the TRCs at the secondary sites show that extravasation and formation of micrometastases by TRCs are more efficient than by the control cells. Remarkably, efficient extravasation of TRCs in vivo and transmigration in vitro are determined by TRC deformability, as a result of low Cdc42 and high Sox2. Our findings suggest that tumor cell deformability is a key factor in controlling extravasation dynamics during metastasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping