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Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched
Despite the development of new therapeutic strategies, cancer remains one of the leading causes of mortality worldwide. One of the current major challenges is the resistance of cancers to chemotherapy treatments inducing metastases and relapse of the tumor. The Hedgehog receptor Patched (Ptch1) is o...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146430/ https://www.ncbi.nlm.nih.gov/pubmed/35631574 http://dx.doi.org/10.3390/pharmaceutics14050988 |
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author | Feliz Morel, Álvaro Javier Hasanovic, Anida Morin, Aurélie Prunier, Chloé Magnone, Virginie Lebrigand, Kevin Aouad, Amaury Cogoluegnes, Sarah Favier, Judith Pasquier, Claude Mus-Veteau, Isabelle |
author_facet | Feliz Morel, Álvaro Javier Hasanovic, Anida Morin, Aurélie Prunier, Chloé Magnone, Virginie Lebrigand, Kevin Aouad, Amaury Cogoluegnes, Sarah Favier, Judith Pasquier, Claude Mus-Veteau, Isabelle |
author_sort | Feliz Morel, Álvaro Javier |
collection | PubMed |
description | Despite the development of new therapeutic strategies, cancer remains one of the leading causes of mortality worldwide. One of the current major challenges is the resistance of cancers to chemotherapy treatments inducing metastases and relapse of the tumor. The Hedgehog receptor Patched (Ptch1) is overexpressed in many types of cancers. We showed that Ptch1 contributes to the efflux of doxorubicin and plays an important role in the resistance to chemotherapy in adrenocortical carcinoma (ACC), a rare cancer which presents strong resistance to the standard of care chemotherapy treatment. In the present study, we isolated and characterized a subpopulation of the ACC cell line H295R in which Ptch1 is overexpressed and more present at the cell surface. This cell subpopulation is more resistant to doxorubicin, grows as spheroids, and has a greater capability of clonogenicity, migration, and invasion than the parental cells. Xenograft experiments performed in mice and in ovo showed that this cell subpopulation is more tumorigenic and metastatic than the parental cells. These results suggest that this cell subpopulation has cancer stem-like or persistent cell properties which were strengthened by RNA-seq. If present in tumors from ACC patients, these cells could be responsible for therapy resistance, relapse, and metastases. |
format | Online Article Text |
id | pubmed-9146430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91464302022-05-29 Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched Feliz Morel, Álvaro Javier Hasanovic, Anida Morin, Aurélie Prunier, Chloé Magnone, Virginie Lebrigand, Kevin Aouad, Amaury Cogoluegnes, Sarah Favier, Judith Pasquier, Claude Mus-Veteau, Isabelle Pharmaceutics Article Despite the development of new therapeutic strategies, cancer remains one of the leading causes of mortality worldwide. One of the current major challenges is the resistance of cancers to chemotherapy treatments inducing metastases and relapse of the tumor. The Hedgehog receptor Patched (Ptch1) is overexpressed in many types of cancers. We showed that Ptch1 contributes to the efflux of doxorubicin and plays an important role in the resistance to chemotherapy in adrenocortical carcinoma (ACC), a rare cancer which presents strong resistance to the standard of care chemotherapy treatment. In the present study, we isolated and characterized a subpopulation of the ACC cell line H295R in which Ptch1 is overexpressed and more present at the cell surface. This cell subpopulation is more resistant to doxorubicin, grows as spheroids, and has a greater capability of clonogenicity, migration, and invasion than the parental cells. Xenograft experiments performed in mice and in ovo showed that this cell subpopulation is more tumorigenic and metastatic than the parental cells. These results suggest that this cell subpopulation has cancer stem-like or persistent cell properties which were strengthened by RNA-seq. If present in tumors from ACC patients, these cells could be responsible for therapy resistance, relapse, and metastases. MDPI 2022-05-05 /pmc/articles/PMC9146430/ /pubmed/35631574 http://dx.doi.org/10.3390/pharmaceutics14050988 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Feliz Morel, Álvaro Javier Hasanovic, Anida Morin, Aurélie Prunier, Chloé Magnone, Virginie Lebrigand, Kevin Aouad, Amaury Cogoluegnes, Sarah Favier, Judith Pasquier, Claude Mus-Veteau, Isabelle Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched |
title | Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched |
title_full | Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched |
title_fullStr | Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched |
title_full_unstemmed | Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched |
title_short | Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched |
title_sort | persistent properties of a subpopulation of cancer cells overexpressing the hedgehog receptor patched |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146430/ https://www.ncbi.nlm.nih.gov/pubmed/35631574 http://dx.doi.org/10.3390/pharmaceutics14050988 |
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