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Patient Derived Cell Culture and Isolation of CD133+ Putative Cancer Stem Cells from Melanoma
Published on: March 13, 2013
Efficient tumour formation by single human melanoma cells.
Elsa Quintana1, Mark Shackleton, Michael S Sabel
1Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, and Center for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109-2216, USA.
Nature
|December 5, 2008
Summary
Tumorigenic potential in human melanoma cells is common, not rare. Modified xenotransplantation assays using highly immunocompromised mice revealed that up to 27% of melanoma cells can form tumors, challenging previous estimates.
Area of Science:
- Cancer Biology
- Immunology
- Genetics
Background:
- A key question in cancer biology is the prevalence of tumorigenic cells within human cancers.
- Previous studies using non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice suggested rare cancer cells (0.1-0.0001%) possess tumor-forming potential.
- The degree to which NOD/SCID mice underestimate tumorigenic cell frequency remained uncertain.
Purpose of the Study:
- To re-evaluate the frequency of tumorigenic cells in human melanomas.
- To investigate if modified xenotransplantation conditions can increase the detection of tumorigenic melanoma cells.
- To determine if tumorigenic cells are common or rare in human melanomas.
Main Methods:
- Utilized modified xenotransplantation assays with highly immunocompromised NOD/SCID interleukin-2 receptor gamma chain null (Il2rg(-/-)) mice.
- Performed limiting dilution assays on melanoma cells from 12 different patients.
- Conducted single-cell transplant experiments with melanoma cells from four patients.
Main Results:
- Modified assay conditions increased the detection of tumorigenic melanoma cells by several orders of magnitude.
- Approximately 25% of unselected melanoma cells from 12 patients formed tumors in modified assays.
- An average of 27% of unselected melanoma cells from four patients formed tumors in single-cell transplants.
Conclusions:
- Tumorigenic cells are common, not rare, in some human cancers like melanoma.
- Previous estimates of tumorigenic cell frequency were significantly underestimated due to assay limitations.
- Enhanced xenotransplantation models are crucial for accurately assessing cancer cell tumorigenicity.
