Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis.
<h4>Background</h4>Alterations in the stem cell niche are likely to contribute to tumorigenesis; however, the concept of niche promoted benign tumor growth remains to be explored. Here we use keloid, an exuberant fibroproliferative dermal growth unique to human skin, as a model to charac...
Guardado en:
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2009
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/1b9261e734e8482788ac67ea1899ff57 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:1b9261e734e8482788ac67ea1899ff57 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:1b9261e734e8482788ac67ea1899ff572021-11-25T06:28:12ZTumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis.1932-620310.1371/journal.pone.0007798https://doaj.org/article/1b9261e734e8482788ac67ea1899ff572009-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19907660/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Alterations in the stem cell niche are likely to contribute to tumorigenesis; however, the concept of niche promoted benign tumor growth remains to be explored. Here we use keloid, an exuberant fibroproliferative dermal growth unique to human skin, as a model to characterize benign tumor-like stem cells and delineate the role of their "pathological" niche in the development of the benign tumor.<h4>Methods and findings</h4>Subclonal assay, flow cytometric and multipotent differentiation analyses demonstrate that keloid contains a new population of stem cells, named keloid derived precursor cells (KPCs), which exhibit clonogenicity, self-renewal, distinct embryonic and mesenchymal stem cell surface markers, and multipotent differentiation. KPCs display elevated telomerase activity and an inherently upregulated proliferation capability as compared to their peripheral normal skin counterparts. A robust elevation of IL-6 and IL-17 expression in keloid is confirmed by cytokine array, western blot and ELISA analyses. The altered biological functions are tightly regulated by the inflammatory niche mediated by an autocrine/paracrine cytokine IL-17/IL-6 axis. Utilizing KPCs transplanted subcutaneously in immunocompromised mice we generate for the first time a human keloid-like tumor model that is driven by the in vivo inflammatory niche and allows testing of the anti-tumor therapeutic effect of antibodies targeting distinct niche components, specifically IL-6 and IL-17.<h4>Conclusions/significance</h4>These findings support our hypothesis that the altered niche in keloids, predominantly inflammatory, contributes to the acquirement of a benign tumor-like stem cell phenotype of KPCs characterized by the uncontrolled self-renewal and increased proliferation, supporting the rationale for in vivo modification of the "pathological" stem cell niche as a novel therapy for keloid and other mesenchymal benign tumors.Qunzhou ZhangTakayoshi YamazaA Paul KellyShihong ShiSonglin WangJimmy BrownLina WangSamuel W FrenchSongtao ShiAnh D LePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 11, p e7798 (2009) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Qunzhou Zhang Takayoshi Yamaza A Paul Kelly Shihong Shi Songlin Wang Jimmy Brown Lina Wang Samuel W French Songtao Shi Anh D Le Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis. |
| description |
<h4>Background</h4>Alterations in the stem cell niche are likely to contribute to tumorigenesis; however, the concept of niche promoted benign tumor growth remains to be explored. Here we use keloid, an exuberant fibroproliferative dermal growth unique to human skin, as a model to characterize benign tumor-like stem cells and delineate the role of their "pathological" niche in the development of the benign tumor.<h4>Methods and findings</h4>Subclonal assay, flow cytometric and multipotent differentiation analyses demonstrate that keloid contains a new population of stem cells, named keloid derived precursor cells (KPCs), which exhibit clonogenicity, self-renewal, distinct embryonic and mesenchymal stem cell surface markers, and multipotent differentiation. KPCs display elevated telomerase activity and an inherently upregulated proliferation capability as compared to their peripheral normal skin counterparts. A robust elevation of IL-6 and IL-17 expression in keloid is confirmed by cytokine array, western blot and ELISA analyses. The altered biological functions are tightly regulated by the inflammatory niche mediated by an autocrine/paracrine cytokine IL-17/IL-6 axis. Utilizing KPCs transplanted subcutaneously in immunocompromised mice we generate for the first time a human keloid-like tumor model that is driven by the in vivo inflammatory niche and allows testing of the anti-tumor therapeutic effect of antibodies targeting distinct niche components, specifically IL-6 and IL-17.<h4>Conclusions/significance</h4>These findings support our hypothesis that the altered niche in keloids, predominantly inflammatory, contributes to the acquirement of a benign tumor-like stem cell phenotype of KPCs characterized by the uncontrolled self-renewal and increased proliferation, supporting the rationale for in vivo modification of the "pathological" stem cell niche as a novel therapy for keloid and other mesenchymal benign tumors. |
| format |
article |
| author |
Qunzhou Zhang Takayoshi Yamaza A Paul Kelly Shihong Shi Songlin Wang Jimmy Brown Lina Wang Samuel W French Songtao Shi Anh D Le |
| author_facet |
Qunzhou Zhang Takayoshi Yamaza A Paul Kelly Shihong Shi Songlin Wang Jimmy Brown Lina Wang Samuel W French Songtao Shi Anh D Le |
| author_sort |
Qunzhou Zhang |
| title |
Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis. |
| title_short |
Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis. |
| title_full |
Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis. |
| title_fullStr |
Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis. |
| title_full_unstemmed |
Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis. |
| title_sort |
tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by il-17/il-6 axis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2009 |
| url |
https://doaj.org/article/1b9261e734e8482788ac67ea1899ff57 |
| work_keys_str_mv |
AT qunzhouzhang tumorlikestemcellsderivedfromhumankeloidaregovernedbytheinflammatorynichedrivenbyil17il6axis AT takayoshiyamaza tumorlikestemcellsderivedfromhumankeloidaregovernedbytheinflammatorynichedrivenbyil17il6axis AT apaulkelly tumorlikestemcellsderivedfromhumankeloidaregovernedbytheinflammatorynichedrivenbyil17il6axis AT shihongshi tumorlikestemcellsderivedfromhumankeloidaregovernedbytheinflammatorynichedrivenbyil17il6axis AT songlinwang tumorlikestemcellsderivedfromhumankeloidaregovernedbytheinflammatorynichedrivenbyil17il6axis AT jimmybrown tumorlikestemcellsderivedfromhumankeloidaregovernedbytheinflammatorynichedrivenbyil17il6axis AT linawang tumorlikestemcellsderivedfromhumankeloidaregovernedbytheinflammatorynichedrivenbyil17il6axis AT samuelwfrench tumorlikestemcellsderivedfromhumankeloidaregovernedbytheinflammatorynichedrivenbyil17il6axis AT songtaoshi tumorlikestemcellsderivedfromhumankeloidaregovernedbytheinflammatorynichedrivenbyil17il6axis AT anhdle tumorlikestemcellsderivedfromhumankeloidaregovernedbytheinflammatorynichedrivenbyil17il6axis |
| _version_ |
1718413666666151936 |