A CD24+CD271+ melanoma cancer stem cell possesses hybrid characteristics of its single marker counterparts and promotes invasion and therapeutic resistance
Abstract Background An important role for phenotype switching has been demonstrated in metastasis and therapeutic resistance of both melanoma and epithelial tumours. Phenotype switching in epithelial tumours is driven by a minority cancer stem cell (CSC) sub-population with lineage plasticity, but s...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-08-01
|
| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-025-02336-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849331668963295232 |
|---|---|
| author | Olivia Knowles Patricio Doldan Isabella Hillier-Richardson Sophia Lunetto Stephanie Lunt Gehad Youssef Luke Gammon Ian C. Mackenzie Michael P. Philpott Hasan Rizvi Daniele Bergamaschi Catherine A. Harwood Adrian Biddle |
| author_facet | Olivia Knowles Patricio Doldan Isabella Hillier-Richardson Sophia Lunetto Stephanie Lunt Gehad Youssef Luke Gammon Ian C. Mackenzie Michael P. Philpott Hasan Rizvi Daniele Bergamaschi Catherine A. Harwood Adrian Biddle |
| author_sort | Olivia Knowles |
| collection | DOAJ |
| description | Abstract Background An important role for phenotype switching has been demonstrated in metastasis and therapeutic resistance of both melanoma and epithelial tumours. Phenotype switching in epithelial tumours is driven by a minority cancer stem cell (CSC) sub-population with lineage plasticity, but such a sub-population has not been identified in melanoma. We investigated whether cell surface markers used to identify CSCs in epithelial tumours could identify a CSC sub-population with lineage plasticity in melanoma. Results We identified a CD24+CD271+ minority sub-population in melanoma that possesses the stem cell characteristics of lineage plasticity and self-renewal. This population displayed hybrid characteristics, combining the attributes of discrete CD24+CD271- and CD24-CD271+ cellular sub-populations but with heightened sphere formation, lineage plasticity, migratory ability and drug resistance over its single-marker counterparts. CD24+CD271- and CD24+CD271+ stem cell sub-populations were observed in 10% of human melanomas, mainly at the invasive front. They were also found in human tumour scRNAseq datasets, where they expressed genes associated with stem cells and therapeutic resistance. The CD24-CD271+ sub-population, on the other hand, shared expression of epithelial-mesenchymal transition (EMT) genes with the CD24+CD271+ sub-population. Conclusions The lack of CD24+CD271- and CD24+CD271+ stem cells in the majority of human melanoma specimens led us to conclude that they may be dispensable for melanoma progression. Nevertheless, the enhanced sphere formation, lineage plasticity, migratory ability and drug resistance of the CD24+CD271+ sub-population may signal a contextual requirement for these stem cells when melanomas face challenging environments both clinically and in experimental systems. |
| format | Article |
| id | doaj-art-2c22f5e5ca4d42dcb70b2eca4e865284 |
| institution | Kabale University |
| issn | 1741-7007 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj-art-2c22f5e5ca4d42dcb70b2eca4e8652842025-08-20T03:46:27ZengBMCBMC Biology1741-70072025-08-0123111510.1186/s12915-025-02336-2A CD24+CD271+ melanoma cancer stem cell possesses hybrid characteristics of its single marker counterparts and promotes invasion and therapeutic resistanceOlivia Knowles0Patricio Doldan1Isabella Hillier-Richardson2Sophia Lunetto3Stephanie Lunt4Gehad Youssef5Luke Gammon6Ian C. Mackenzie7Michael P. Philpott8Hasan Rizvi9Daniele Bergamaschi10Catherine A. Harwood11Adrian Biddle12Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonCentre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonCentre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonCentre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonCentre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonCentre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonCentre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonCentre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonCentre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonDepartment of Cellular Pathology, Barts Health NHS TrustCentre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonCentre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonCentre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonAbstract Background An important role for phenotype switching has been demonstrated in metastasis and therapeutic resistance of both melanoma and epithelial tumours. Phenotype switching in epithelial tumours is driven by a minority cancer stem cell (CSC) sub-population with lineage plasticity, but such a sub-population has not been identified in melanoma. We investigated whether cell surface markers used to identify CSCs in epithelial tumours could identify a CSC sub-population with lineage plasticity in melanoma. Results We identified a CD24+CD271+ minority sub-population in melanoma that possesses the stem cell characteristics of lineage plasticity and self-renewal. This population displayed hybrid characteristics, combining the attributes of discrete CD24+CD271- and CD24-CD271+ cellular sub-populations but with heightened sphere formation, lineage plasticity, migratory ability and drug resistance over its single-marker counterparts. CD24+CD271- and CD24+CD271+ stem cell sub-populations were observed in 10% of human melanomas, mainly at the invasive front. They were also found in human tumour scRNAseq datasets, where they expressed genes associated with stem cells and therapeutic resistance. The CD24-CD271+ sub-population, on the other hand, shared expression of epithelial-mesenchymal transition (EMT) genes with the CD24+CD271+ sub-population. Conclusions The lack of CD24+CD271- and CD24+CD271+ stem cells in the majority of human melanoma specimens led us to conclude that they may be dispensable for melanoma progression. Nevertheless, the enhanced sphere formation, lineage plasticity, migratory ability and drug resistance of the CD24+CD271+ sub-population may signal a contextual requirement for these stem cells when melanomas face challenging environments both clinically and in experimental systems.https://doi.org/10.1186/s12915-025-02336-2MelanomaCancer stem cellsCD24Therapy resistance |
| spellingShingle | Olivia Knowles Patricio Doldan Isabella Hillier-Richardson Sophia Lunetto Stephanie Lunt Gehad Youssef Luke Gammon Ian C. Mackenzie Michael P. Philpott Hasan Rizvi Daniele Bergamaschi Catherine A. Harwood Adrian Biddle A CD24+CD271+ melanoma cancer stem cell possesses hybrid characteristics of its single marker counterparts and promotes invasion and therapeutic resistance BMC Biology Melanoma Cancer stem cells CD24 Therapy resistance |
| title | A CD24+CD271+ melanoma cancer stem cell possesses hybrid characteristics of its single marker counterparts and promotes invasion and therapeutic resistance |
| title_full | A CD24+CD271+ melanoma cancer stem cell possesses hybrid characteristics of its single marker counterparts and promotes invasion and therapeutic resistance |
| title_fullStr | A CD24+CD271+ melanoma cancer stem cell possesses hybrid characteristics of its single marker counterparts and promotes invasion and therapeutic resistance |
| title_full_unstemmed | A CD24+CD271+ melanoma cancer stem cell possesses hybrid characteristics of its single marker counterparts and promotes invasion and therapeutic resistance |
| title_short | A CD24+CD271+ melanoma cancer stem cell possesses hybrid characteristics of its single marker counterparts and promotes invasion and therapeutic resistance |
| title_sort | cd24 cd271 melanoma cancer stem cell possesses hybrid characteristics of its single marker counterparts and promotes invasion and therapeutic resistance |
| topic | Melanoma Cancer stem cells CD24 Therapy resistance |
| url | https://doi.org/10.1186/s12915-025-02336-2 |
| work_keys_str_mv | AT oliviaknowles acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT patriciodoldan acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT isabellahillierrichardson acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT sophialunetto acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT stephanielunt acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT gehadyoussef acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT lukegammon acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT iancmackenzie acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT michaelpphilpott acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT hasanrizvi acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT danielebergamaschi acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT catherineaharwood acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT adrianbiddle acd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT oliviaknowles cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT patriciodoldan cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT isabellahillierrichardson cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT sophialunetto cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT stephanielunt cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT gehadyoussef cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT lukegammon cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT iancmackenzie cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT michaelpphilpott cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT hasanrizvi cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT danielebergamaschi cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT catherineaharwood cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance AT adrianbiddle cd24cd271melanomacancerstemcellpossesseshybridcharacteristicsofitssinglemarkercounterpartsandpromotesinvasionandtherapeuticresistance |