True cancer stem cells exhibit relative degrees of dormancy and genomic stability
Background: Cancer stem cells in human tumors have been defined by stem cell markers, embryonal signaling pathways and characteristic biology, ie., namely the ability to repopulate the proliferating population. However, even if these properties can be demonstrated within a tumor cell subpopulation,...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558625000065 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832557593203048448 |
|---|---|
| author | Sanford H. Barsky Krista Mcphail Justin Wang Jordan Dillard Crystal J. Beard Yin Ye |
| author_facet | Sanford H. Barsky Krista Mcphail Justin Wang Jordan Dillard Crystal J. Beard Yin Ye |
| author_sort | Sanford H. Barsky |
| collection | DOAJ |
| description | Background: Cancer stem cells in human tumors have been defined by stem cell markers, embryonal signaling pathways and characteristic biology, ie., namely the ability to repopulate the proliferating population. However, even if these properties can be demonstrated within a tumor cell subpopulation, it does not mean that they are truly hierarchical stem cells because they could have been derived from the proliferating population in a reversible manner. Methods: Using a human PDX, Mary-X, that overall expressed a strong cancer stem cell phenotype, the study conducted both GPP-labelled retroviral transfection and fluorescent microsphere uptake studies to distinguish proliferating from dormant cells and array CGH to identify regions of amplifications (gains) and deletions (losses) on the overall Mary-X population and then applied derived probes by FISH on individual cells to identify a genomically stable subpopulation. Results: Whereas 97-99 % of the cells expressed retroviral GFP and not fluorescent particles and showed numerous gene amplifications and deletions, approximately 1-3 % of the cells showed the opposite. The subpopulation with the retained fluorescent microspheres and exhibiting genomic stability was significantly smaller in size than their GFP-expressing and genomically unstable counterparts. Sorting Mary-X spheroids on the basis of either CD133 or ALDH positivity further enriched for this subpopulation. Conclusions: These studies indicate that a truly biological cancer stem cell subpopulation exists that exhibits both dormancy and genomic stability. This subpopulation could not have been derived from the proliferating and resulting genomically unstable population and therefore represents a truly hierarchical stem cell subpopulation capable of only unidirectional differentiation. |
| format | Article |
| id | doaj-art-a9790275e4b84dd68a4cbae257ce3dd5 |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-a9790275e4b84dd68a4cbae257ce3dd52025-02-03T04:16:37ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-02-0160101127True cancer stem cells exhibit relative degrees of dormancy and genomic stabilitySanford H. Barsky0Krista Mcphail1Justin Wang2Jordan Dillard3Crystal J. Beard4Yin Ye5Department of Pathology, Anatomy and Cell Biology and the Clinical and Translational Research Center of Excellence, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN 37208, USA; Corresponding author.Star Diagnostics Laboratories, 215 E Warm Springs Rd, Ste 108, Las Vegas, NV 89119, USAScripps Mercy Hospital, MER 35, San Diego, CA 92103, USADepartment of Pathology, Anatomy and Cell Biology and the Clinical and Translational Research Center of Excellence, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN 37208, USADepartment of Pathology, Anatomy and Cell Biology and the Clinical and Translational Research Center of Excellence, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN 37208, USADepartment of Pathology, Anatomy and Cell Biology and the Clinical and Translational Research Center of Excellence, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN 37208, USABackground: Cancer stem cells in human tumors have been defined by stem cell markers, embryonal signaling pathways and characteristic biology, ie., namely the ability to repopulate the proliferating population. However, even if these properties can be demonstrated within a tumor cell subpopulation, it does not mean that they are truly hierarchical stem cells because they could have been derived from the proliferating population in a reversible manner. Methods: Using a human PDX, Mary-X, that overall expressed a strong cancer stem cell phenotype, the study conducted both GPP-labelled retroviral transfection and fluorescent microsphere uptake studies to distinguish proliferating from dormant cells and array CGH to identify regions of amplifications (gains) and deletions (losses) on the overall Mary-X population and then applied derived probes by FISH on individual cells to identify a genomically stable subpopulation. Results: Whereas 97-99 % of the cells expressed retroviral GFP and not fluorescent particles and showed numerous gene amplifications and deletions, approximately 1-3 % of the cells showed the opposite. The subpopulation with the retained fluorescent microspheres and exhibiting genomic stability was significantly smaller in size than their GFP-expressing and genomically unstable counterparts. Sorting Mary-X spheroids on the basis of either CD133 or ALDH positivity further enriched for this subpopulation. Conclusions: These studies indicate that a truly biological cancer stem cell subpopulation exists that exhibits both dormancy and genomic stability. This subpopulation could not have been derived from the proliferating and resulting genomically unstable population and therefore represents a truly hierarchical stem cell subpopulation capable of only unidirectional differentiation.http://www.sciencedirect.com/science/article/pii/S1476558625000065Cancer stem cellsArray CGHGenomic instabilityGene amplificationsGene deletionsParticle uptake |
| spellingShingle | Sanford H. Barsky Krista Mcphail Justin Wang Jordan Dillard Crystal J. Beard Yin Ye True cancer stem cells exhibit relative degrees of dormancy and genomic stability Neoplasia: An International Journal for Oncology Research Cancer stem cells Array CGH Genomic instability Gene amplifications Gene deletions Particle uptake |
| title | True cancer stem cells exhibit relative degrees of dormancy and genomic stability |
| title_full | True cancer stem cells exhibit relative degrees of dormancy and genomic stability |
| title_fullStr | True cancer stem cells exhibit relative degrees of dormancy and genomic stability |
| title_full_unstemmed | True cancer stem cells exhibit relative degrees of dormancy and genomic stability |
| title_short | True cancer stem cells exhibit relative degrees of dormancy and genomic stability |
| title_sort | true cancer stem cells exhibit relative degrees of dormancy and genomic stability |
| topic | Cancer stem cells Array CGH Genomic instability Gene amplifications Gene deletions Particle uptake |
| url | http://www.sciencedirect.com/science/article/pii/S1476558625000065 |
| work_keys_str_mv | AT sanfordhbarsky truecancerstemcellsexhibitrelativedegreesofdormancyandgenomicstability AT kristamcphail truecancerstemcellsexhibitrelativedegreesofdormancyandgenomicstability AT justinwang truecancerstemcellsexhibitrelativedegreesofdormancyandgenomicstability AT jordandillard truecancerstemcellsexhibitrelativedegreesofdormancyandgenomicstability AT crystaljbeard truecancerstemcellsexhibitrelativedegreesofdormancyandgenomicstability AT yinye truecancerstemcellsexhibitrelativedegreesofdormancyandgenomicstability |