PUBLICATION
Heterogeneous Tumor Subpopulations Cooperate to Drive Invasion
- Authors
- Chapman, A., Fernandez Del Ama, L., Ferguson, J., Kamarashev, J., Wellbrock, C., Hurlstone, A.
- ID
- ZDB-PUB-140730-12
- Date
- 2014
- Source
- Cell Reports 8(3): 688-695 (Journal)
- Registered Authors
- Hurlstone, Adam
- Keywords
- none
- MeSH Terms
-
- Neoplasm Invasiveness
- Melanoma/metabolism
- Melanoma/pathology*
- Microphthalmia-Associated Transcription Factor/genetics
- Microphthalmia-Associated Transcription Factor/metabolism
- Matrix Metalloproteinase 14/genetics
- Matrix Metalloproteinase 14/metabolism
- Cellular Reprogramming*
- Humans
- Zebrafish
- Animals
- Phenotype
- Melanocytes/classification
- Melanocytes/physiology
- Cell Line, Tumor
- Cell Movement*
- Extracellular Matrix/metabolism
- PubMed
- 25066122 Full text @ Cell Rep.
Citation
Chapman, A., Fernandez Del Ama, L., Ferguson, J., Kamarashev, J., Wellbrock, C., Hurlstone, A. (2014) Heterogeneous Tumor Subpopulations Cooperate to Drive Invasion. Cell Reports. 8(3):688-695.
Abstract
Clonal selection and transcriptional reprogramming (e.g., epithelial-mesenchymal transition or phenotype switching) are the predominant theories thought to underlie tumor progression. However, a "division of labor" leading to cooperation among tumor-cell subpopulations could be an additional catalyst of progression. Using a zebrafish-melanoma xenograft model, we found that in a heterogeneous setting, inherently invasive cells, which possess protease activity and deposit extracellular matrix (ECM), co-invade with subpopulations of poorly invasive cells, a phenomenon we term "cooperative invasion". Whereas the poorly invasive cells benefit from heterogeneity, the invasive cells switch from protease-independent to an MT1-MMP-dependent mode of invasion. We did not observe changes in expression of the melanoma phenotype determinant MITF during cooperative invasion, thus ruling out the necessity for phenotype switching for invasion. Altogether, our data suggest that cooperation can drive melanoma progression without the need for clonal selection or phenotype switching and can account for the preservation of heterogeneity seen throughout tumor progression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping