Melanoma chemotherapy leads to the selection of ABCB5-expressing cells.

Article Details

Citation

Chartrain M, Riond J, Stennevin A, Vandenberghe I, Gomes B, Lamant L, Meyer N, Gairin JE, Guilbaud N, Annereau JP

Melanoma chemotherapy leads to the selection of ABCB5-expressing cells.

PLoS One. 2012;7(5):e36762. doi: 10.1371/journal.pone.0036762. Epub 2012 May 24.

PubMed ID
22675422 [ View in PubMed
]
Abstract

Metastatic melanoma is the most aggressive skin cancer. Recently, phenotypically distinct subpopulations of tumor cells were identified. Among them, ABCB5-expressing cells were proposed to display an enhanced tumorigenicity with stem cell-like properties. In addition, ABCB5(+) cells are thought to participate to chemoresistance through a potential efflux function of ABCB5. Nevertheless, the fate of these cells upon drugs that are used in melanoma chemotherapy remains to be clarified. Here we explored the effect of anti-melanoma treatments on the ABCB5-expressing cells. Using a melanoma xenograft model (WM266-4), we observed in vivo that ABCB5-expressing cells are enriched after a temozolomide treatment that induces a significant tumor regression. These results were further confirmed in a preliminary study conducted on clinical samples from patients that received dacarbazine. In vitro, we showed that ABCB5-expressing cells selectively survive when exposed to dacarbazine, the reference treatment of metastatic melanoma, but also to vemurafenib, a new inhibitor of the mutated kinase V600E BRAF and other various chemotherapeutic drugs. Our results show that anti-melanoma chemotherapy might participate to the chemoresistance acquisition by selecting tumor cell subpopulations expressing ABCB5. This is of particular importance in understanding the relapses observed after anti-melanoma treatments and reinforces the interest of ABCB5 and ABCB5-expressing cells as potential therapeutic targets in melanoma.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
ATP-binding cassette sub-family B member 5Q2M3G0Details