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Article

Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched

1
Université Côte d’Azur, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), 06560 Valbonne, France
2
Université de Paris, PARCC, INSERM, Equipe Labellisée par la Ligue Contre le Cancer, CEDEX 15, 75737 Paris, France
3
INOVOTION, Biopolis-5 Av. du Grand Sablon, 38700 La Tronche, France
4
Université Côte d’Azur, CNRS-UMR7271, Laboratoire d’Informatique, Signaux et Systèmes de Sophia Antipolis (I3S), 06560 Valbonne, France
*
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
Academic Editor: Hassan Bousbaa
Pharmaceutics 2022, 14(5), 988; https://doi.org/10.3390/pharmaceutics14050988
Received: 19 January 2022 / Revised: 22 April 2022 / Accepted: 29 April 2022 / Published: 5 May 2022
(This article belongs to the Special Issue Novel Anticancer Strategies (Volume II))
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. View Full-Text
Keywords: Patched; chemotherapy resistance; metastases; cancer stem cells; persistent cells; adrenocortical carcinoma Patched; chemotherapy resistance; metastases; cancer stem cells; persistent cells; adrenocortical carcinoma
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MDPI and ACS Style

Feliz Morel, Á.J.; Hasanovic, A.; Morin, A.; Prunier, C.; Magnone, V.; Lebrigand, K.; Aouad, A.; Cogoluegnes, S.; Favier, J.; Pasquier, C.; Mus-Veteau, I. Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched. Pharmaceutics 2022, 14, 988. https://doi.org/10.3390/pharmaceutics14050988

AMA Style

Feliz Morel ÁJ, Hasanovic A, Morin A, Prunier C, Magnone V, Lebrigand K, Aouad A, Cogoluegnes S, Favier J, Pasquier C, Mus-Veteau I. Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched. Pharmaceutics. 2022; 14(5):988. https://doi.org/10.3390/pharmaceutics14050988

Chicago/Turabian Style

Feliz Morel, Álvaro J., Anida Hasanovic, Aurélie Morin, Chloé Prunier, Virginie Magnone, Kevin Lebrigand, Amaury Aouad, Sarah Cogoluegnes, Judith Favier, Claude Pasquier, and Isabelle Mus-Veteau. 2022. "Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched" Pharmaceutics 14, no. 5: 988. https://doi.org/10.3390/pharmaceutics14050988

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