BoneKEy Reports | BoneKEy Watch

Cellular plasticity and metastatic potential



DOI:10.1038/bonekey.2012.139

Tumor initiating cells are an important component of the complex pathway that establishes a metastatic tumor. As cells change from normal to neoplastic, they become capable of unlimited self-renewal and they are more able to survive under stress. To determine the relationship between cancer stem cells and cells with an epithelial or mesenchymal phenotype, this study generated and compared two cell populations derived from the same parent prostate cancer cell line, PC-3.

One cell line exhibited a strong epithelial phenotype, expressing E-cadherin, desmoplakin and genes that are known to confer self renewal and pluripotency. This line had a high level of tumor-initiating cells that were highly metastatic. The other cell line had a mesenchymal phenotype, expressing many mesenchymal markers and genes for inflammatory chemokines and their receptors, indicating an ability to withstand physiological stress. However, the mesenchymal cell line had far fewer tumor-initiating cells.

Knock down of key gene programs in two cell lines allowed conversion of the epithelial phenotype to the mesenchymal phenotype and vice versa. The authors suggest that the two cell types might cooperate in vivo to allow plasticity and therefore maximum metastatic potential.

Editor's comment: This study provides new insights into the plasticity of cancer progression. The authors show that programs controlling epithelial-to-mesenchymal transition, which enhance local invasiveness of cancer cells, can suppress those controlling cancer stem cell-like properties that allow metastasis to distant organs.


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