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Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells
Published on: October 20, 2015
Tumorigenic potential of circulating prostate tumor cells
Filipe L F Carvalho1, Brian W Simons, Emmanuel S Antonarakis
1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Oncotarget
|March 27, 2013
Summary
Viable circulating tumor cells (CTCs) were isolated from mice and humans without size bias. Mouse CTCs initiated tumors in mice, but human CTCs did not, suggesting most CTCs have low tumor-forming potential.
Area of Science:
- Oncology
- Cancer Metastasis
- Cell Biology
Background:
- Circulating tumor cells (CTCs) are crucial for metastasis but their tumor-forming potential is largely untested.
- Current isolation methods often select for non-viable cells, hindering research into CTCs' tumorigenicity.
- A need exists for methods that isolate viable CTCs for functional assays.
Purpose of the Study:
- To isolate viable prostate CTCs from mice and humans without relying on cell size or differentiation markers.
- To assess the tumor-initiating capacity of isolated viable CTCs in immunodeficient mice.
Main Methods:
- Blood from TRAMP mice and prostate cancer patients was processed using gradient density centrifugation and CD45 magnetic depletion.
- Isolated CTCs were verified using immunocytochemistry (cytokeratin 8, EpCAM).
- CTCs were inoculated into immunodeficient mice to monitor tumor formation.
Main Results:
- Viable CTCs were isolated from mice without size or surface marker bias.
- Two of nine mice inoculated with TRAMP CTCs developed liver metastases.
- Human CTCs were identified but did not form tumors in mice.
Conclusions:
- Viable, tumor-initiating CTCs can be isolated using a method independent of epithelial markers or size.
- TRAMP CTCs demonstrated tumorigenicity, confirming the presence of viable tumor-initiating cells.
- The low tumor formation rate suggests most CTCs possess limited tumor-forming potential, highlighting the need to identify highly tumorigenic subsets.
