PUBLICATION

Zebrafish Microenvironment Elevates EMT and CSC-Like Phenotype of Engrafted Prostate Cancer Cells

Authors
Chen, L., Boleslaw Olszewski, M., Kruithof-de Julio, M., Snaar-Jagalska, B.E.
ID
ZDB-PUB-200403-210
Date
2020
Source
Cells   9(4): (Journal)
Registered Authors
Snaar-Jagalska, Ewa B.
Keywords
Zebrafish xenograft model, cell plasticity, prostate cancer
MeSH Terms
  • Administration, Intravenous
  • Aldehyde Dehydrogenase/metabolism
  • Animals
  • Biomarkers, Tumor/metabolism
  • Carcinogenesis/metabolism
  • Carcinogenesis/pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Homeodomain Proteins/metabolism
  • Humans
  • Male
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Neoplastic Stem Cells/pathology*
  • Phenotype
  • Prostatic Neoplasms/pathology*
  • Transcription Factors/metabolism
  • Tumor Microenvironment*
  • Zebrafish/physiology*
  • Zebrafish Proteins/metabolism
PubMed
32225005 Full text @ Cells
Abstract
To visually and genetically trace single-cell dynamics of human prostate cancer (PCa) cells at the early stage of metastasis, a zebrafish (ZF) xenograft model was employed. The phenotypes of intravenously transplanted fluorescent cells were monitored by high-resolution, single-cell intravital confocal and light-sheet imaging. Engrafted osteotropic, androgen independent PCa cells were extravasated from caudle vein, invaded the neighboring tissue, proliferated and formed experimental metastases around caudal hematopoietic tissue (CHT) in four days. Gene expression comparison between cells in culture and in CHT revealed that engrafted PCa cells responded to the ZF microenvironment by elevating expression of epithelial-mesenchymal transition (EMT) and stemness markers. Next, metastatic potentials of ALDHhi cancer stem-like cells (CSCs) and ALDHlow non-CSCs were analyzed in ZF. Engraftment of CSCs induced faster metastatic onset, however after six days both cell subpopulations equally responded to the ZF microenvironment, resulting in the same increase of stemness genes expression including Nanog, Oct-4 and Cripto. Knockdown of Cripto significantly reduced the vimentin/E-cadherin ratio in engrafted cells, indicating that Cripto is required for transduction of the microenvironment signals from the ZF niche to increase mesenchymal potential of cells. Targeting of either Cripto or EMT transcriptional factors Snail 1 and Zeb1 significantly suppressed metastatic growth. These data indicated that zebrafish microenvironment governed the CSC/EMT plasticity of human PCa cells promoting metastasis initiation.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping