Melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function.
<h4>Background</h4>The aggressiveness of melanoma tumors is likely to rely on their well-recognized heterogeneity and plasticity. Melanoma comprises multi-subpopulations of cancer cells some of which may possess stem cell-like properties. Although useful, the sphere-formation assay to id...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2011
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/a36cdd4d0a6a448182064f87b8ed2de0 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:a36cdd4d0a6a448182064f87b8ed2de0 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:a36cdd4d0a6a448182064f87b8ed2de02021-11-18T06:55:40ZMelanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function.1932-620310.1371/journal.pone.0018784https://doaj.org/article/a36cdd4d0a6a448182064f87b8ed2de02011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21526207/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The aggressiveness of melanoma tumors is likely to rely on their well-recognized heterogeneity and plasticity. Melanoma comprises multi-subpopulations of cancer cells some of which may possess stem cell-like properties. Although useful, the sphere-formation assay to identify stem cell-like or tumor initiating cell subpopulations in melanoma has been challenged, and it is unclear if this model can predict a functional phenotype associated with aggressive tumor cells.<h4>Methodology/principal findings</h4>We analyzed the molecular and functional phenotypes of melanoma spheroids formed in neural crest cell medium. Whether from metastatic or advanced primary tumors, spheroid cells expressed melanoma-associated markers. They displayed higher capacity to differentiate along mesenchymal lineages and enhanced expression of SOX2, NANOG, KLF4, and/or OCT4 transcription factors, but not enhanced self-renewal or tumorigenicity when compared to their adherent counterparts. Gene expression profiling attributed a neural crest cell signature to these spheroids and indicated that a migratory/invasive and immune-function modulating program could be associated with these cells. In vitro assays confirmed that spheroids display enhanced migratory/invasive capacities. In immune activation assays, spheroid cells elicited a poorer allogenic response from immune cells and inhibited mitogen-dependent T cells activation and proliferation more efficiently than their adherent counterparts. Our findings reveal a novel immune-modulator function of melanoma spheroids and suggest specific roles for spheroids in invasion and in evasion of antitumor immunity.<h4>Conclusion/significance</h4>The association of a more plastic, invasive and evasive, thus a more aggressive tumor phenotype with melanoma spheroids reveals a previously unrecognized aspect of tumor cells expanded as spheroid cultures. While of limited efficiency for melanoma initiating cell identification, our melanoma spheroid model predicted aggressive phenotype and suggested that aggressiveness and heterogeneity of melanoma tumors can be supported by subpopulations other than cancer stem cells. Therefore, it could be constructive to investigate melanoma aggressiveness, relevant to patients and clinical transferability.Kiran RamgolamJessica LauriolClaude LalouLaura LaudenLaurence MichelPierre de la GrangeAbdel-Majid KhatibFawzi AoudjitDominique CharronCatherine Alcaide-LoridanReem Al-DaccakPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e18784 (2011) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Kiran Ramgolam Jessica Lauriol Claude Lalou Laura Lauden Laurence Michel Pierre de la Grange Abdel-Majid Khatib Fawzi Aoudjit Dominique Charron Catherine Alcaide-Loridan Reem Al-Daccak Melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function. |
| description |
<h4>Background</h4>The aggressiveness of melanoma tumors is likely to rely on their well-recognized heterogeneity and plasticity. Melanoma comprises multi-subpopulations of cancer cells some of which may possess stem cell-like properties. Although useful, the sphere-formation assay to identify stem cell-like or tumor initiating cell subpopulations in melanoma has been challenged, and it is unclear if this model can predict a functional phenotype associated with aggressive tumor cells.<h4>Methodology/principal findings</h4>We analyzed the molecular and functional phenotypes of melanoma spheroids formed in neural crest cell medium. Whether from metastatic or advanced primary tumors, spheroid cells expressed melanoma-associated markers. They displayed higher capacity to differentiate along mesenchymal lineages and enhanced expression of SOX2, NANOG, KLF4, and/or OCT4 transcription factors, but not enhanced self-renewal or tumorigenicity when compared to their adherent counterparts. Gene expression profiling attributed a neural crest cell signature to these spheroids and indicated that a migratory/invasive and immune-function modulating program could be associated with these cells. In vitro assays confirmed that spheroids display enhanced migratory/invasive capacities. In immune activation assays, spheroid cells elicited a poorer allogenic response from immune cells and inhibited mitogen-dependent T cells activation and proliferation more efficiently than their adherent counterparts. Our findings reveal a novel immune-modulator function of melanoma spheroids and suggest specific roles for spheroids in invasion and in evasion of antitumor immunity.<h4>Conclusion/significance</h4>The association of a more plastic, invasive and evasive, thus a more aggressive tumor phenotype with melanoma spheroids reveals a previously unrecognized aspect of tumor cells expanded as spheroid cultures. While of limited efficiency for melanoma initiating cell identification, our melanoma spheroid model predicted aggressive phenotype and suggested that aggressiveness and heterogeneity of melanoma tumors can be supported by subpopulations other than cancer stem cells. Therefore, it could be constructive to investigate melanoma aggressiveness, relevant to patients and clinical transferability. |
| format |
article |
| author |
Kiran Ramgolam Jessica Lauriol Claude Lalou Laura Lauden Laurence Michel Pierre de la Grange Abdel-Majid Khatib Fawzi Aoudjit Dominique Charron Catherine Alcaide-Loridan Reem Al-Daccak |
| author_facet |
Kiran Ramgolam Jessica Lauriol Claude Lalou Laura Lauden Laurence Michel Pierre de la Grange Abdel-Majid Khatib Fawzi Aoudjit Dominique Charron Catherine Alcaide-Loridan Reem Al-Daccak |
| author_sort |
Kiran Ramgolam |
| title |
Melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function. |
| title_short |
Melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function. |
| title_full |
Melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function. |
| title_fullStr |
Melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function. |
| title_full_unstemmed |
Melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function. |
| title_sort |
melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/a36cdd4d0a6a448182064f87b8ed2de0 |
| work_keys_str_mv |
AT kiranramgolam melanomaspheroidsgrownunderneuralcrestcellconditionsarehighlyplasticmigratoryinvasivetumorcellsendowedwithimmunomodulatorfunction AT jessicalauriol melanomaspheroidsgrownunderneuralcrestcellconditionsarehighlyplasticmigratoryinvasivetumorcellsendowedwithimmunomodulatorfunction AT claudelalou melanomaspheroidsgrownunderneuralcrestcellconditionsarehighlyplasticmigratoryinvasivetumorcellsendowedwithimmunomodulatorfunction AT lauralauden melanomaspheroidsgrownunderneuralcrestcellconditionsarehighlyplasticmigratoryinvasivetumorcellsendowedwithimmunomodulatorfunction AT laurencemichel melanomaspheroidsgrownunderneuralcrestcellconditionsarehighlyplasticmigratoryinvasivetumorcellsendowedwithimmunomodulatorfunction AT pierredelagrange melanomaspheroidsgrownunderneuralcrestcellconditionsarehighlyplasticmigratoryinvasivetumorcellsendowedwithimmunomodulatorfunction AT abdelmajidkhatib melanomaspheroidsgrownunderneuralcrestcellconditionsarehighlyplasticmigratoryinvasivetumorcellsendowedwithimmunomodulatorfunction AT fawziaoudjit melanomaspheroidsgrownunderneuralcrestcellconditionsarehighlyplasticmigratoryinvasivetumorcellsendowedwithimmunomodulatorfunction AT dominiquecharron melanomaspheroidsgrownunderneuralcrestcellconditionsarehighlyplasticmigratoryinvasivetumorcellsendowedwithimmunomodulatorfunction AT catherinealcaideloridan melanomaspheroidsgrownunderneuralcrestcellconditionsarehighlyplasticmigratoryinvasivetumorcellsendowedwithimmunomodulatorfunction AT reemaldaccak melanomaspheroidsgrownunderneuralcrestcellconditionsarehighlyplasticmigratoryinvasivetumorcellsendowedwithimmunomodulatorfunction |
| _version_ |
1718424184118312960 |