Abstract
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.
Highlights
Melanomas are very aggressive neoplasms renowned for their resistance to existing therapeutics
The most recent treatments targeting the mutated BRAF (BRAFV600E) have shown a spectacular high level of response, but in most cases melanomas acquire secondary resistances causing dramatic relapses [1]. Both primary and secondary resistances, as well as the exacerbated invasive properties of melanomas might be due to their remarkable phenotypic plasticity, allowing melanoma cells to adapt to different microenvironments and to chemotherapeutic drugs
We wanted to determine if two of the most studied Melanoma Initiating Cell (MIC) markers, ABCB5 and CD271 were shared by the same population or were expressed by different cell populations
Summary
Melanomas are very aggressive neoplasms renowned for their resistance to existing therapeutics. The most recent treatments targeting the mutated BRAF (BRAFV600E) have shown a spectacular high level of response, but in most cases melanomas acquire secondary resistances causing dramatic relapses [1]. Both primary and secondary resistances, as well as the exacerbated invasive properties of melanomas might be due to their remarkable phenotypic plasticity, allowing melanoma cells to adapt to different microenvironments and to chemotherapeutic drugs. The melanoma initiating cell model stems from the initial works of Lapidot et al [2] in leukemia, Singh et al [3] in brain cancer and Ricci-Vitani et al [4] in colon cancer These pioneer works defined tumor initiating cells as cells responsible for tumor formation and maintenance, in vivo, in xenograft models
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
