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

Abstract

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.

A network embedding approach to identify active modules in biological interaction networks

“…The networks we generate, with the parameters presented in this article, are closer to a real interaction network than the networks used by some competing methods. In addition to the results reported in this article, several studies utilizing AMINE to analyze various types of data have already been published (Feliz Morel et al, 2022;Pasquier & Robichon, 2022a;2022b), which also emphasizes the relevance of the results obtained by the method.…”

“…Several studies utilizing AMINE to analyze various types of data have already been published ( Feliz Morel et al, 2022 ; Pasquier & Robichon 2022a ; 2022b ).…”

Novel Anticancer Strategies II

“…Several CSC biomarkers have been identified with useful applications to diagnosis, therapy, and prognosis. The paper by Morel et al described the isolation of a subpopulation of the adrenocortical carcinoma (ACC) cell line H295R overexpressing the cell surface Hedgehog receptor Patched (Ptch1) [ 14 ]. Ptch1 is overexpressed in many cancer types and was shown to contribute to the resistance to chemotherapy in ACC.…”