Understanding the molecular and cellular processes underlying melanoma plasticity and heterogeneity is of paramount importance to improve the efficiency of current treatment and to overcome resistance to chemotherapy drugs.,The notion of plasticity and heterogeneity implies the existence of melanoma cell populations with different phenotypic and tumorigenic properties.,Using melanoma cell lines and melanoma cells freshly isolated from patient biopsies, we investigated the relationship between ABCB5+, CD271+ and low-MITF, expressing populations that were reported to display melanoma initiating cell properties.,Here, we showed that ABCB5+ and CD271+ populations poorly overlap.,However, we found that the CD271+ population is enriched in low-MITF cells and expresses a higher level of stemness genes, such as OCT4, NANOG and NES.,These features could explain the increased tumorigenicity of the CD271+ cells.,The rapid conversion of CD271+ to CD271− cells in vitro demonstrates the plasticity ability of melanoma cells.,Finally, we observed that the transient slow-growing population contains only CD271+ cells that are highly tumorigenic.,However, the fast growing/CD271+ population exhibits a poor tumorigenic ability.,Taking together, our data show that CD271 is an imperfect marker for melanoma initiating cells, but may be useful to identify melanoma cells with an increased stemness and tumorigenic potential.
This study compared the central nervous system (CNS) metastasis incidence between a temozolomide- and a dacarbazine-based regimen in untreated stage IV melanoma patients.,A total of 150 patients were randomly assigned to receive either oral temozolomide (200 mg m−2 per day; days 1-5) or intravenous dacarbazine (800 mg m−2; day 1), in combination with intravenous cisplatin (75 mg m−2; day 1) and subcutaneous interleukin-2 (3 MU twice daily; days 9-18), every 28 days (CTI and CDI).,A total of 149 patients were eligible for an intention-to-treat analysis (CTI: n=74, CDI: n=75).,The 1-year cumulative CNS incidence failure was 20.6% for CTI and 31.1% for CDI (P=0.22).,In all 24 patients in CTI (32%) and 34 (45%) in CDI developed CNS metastases; 31 patients died of early systemic progression, before CNS evaluation.,Median survival time was 8.4 months in the CTI and 8.7 in the CDI arm; in patients with CNS metastases the median survival time was 13.5 months in the CTI and 11.5 in the CDI arm.,No difference in toxicity was observed between the two arms.,The incidence of CNS failures in metastatic melanoma was not significantly reduced and the clinical course was not modified substituting a dacarbazine-based regimen with a temozolomide-based regimen.,Patients who developed CNS metastases did not have a worse prognosis than patients progressing in other sites and should not be excluded from new investigational studies.