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.