CD271 is an imperfect marker for melanoma initiating cells

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.

CD271 Expression on Patient Melanoma Cells Is Unstable and Unlinked to Tumorigenicity

“…Notably and consistent with previous studies (7,10), CD271 was heterogeneously expressed in secondary tumors regardless of the CD271 phenotype of cells that give rise to them (Fig. 5).…”

“…Studies of cell lines also found enriched tumorigenicity among slow-cycling fractions of CD271 þ melanoma cells (7) and a functional role for CD271 in disease propagation (8).…”

CD271 Down-Regulation Promotes Melanoma Progression and Invasion in Three-Dimensional Models and in Zebrafish

“…It has been recently proposed that CD271 is an "imperfect marker" for MICs, as fast growing/CD271 + cells exhibit poor tumorigenic ability (Cheli et al, 2014). To better understand the role of this receptor in melanoma, we studied CD271 in vitro by using 3-dimensional (3D) multicellular spheroids and skin equivalents which closely mimick the behavior of solid tumors in vivo (Griffith and Swarz, 2006).…”

In vitro long-term treatment with MAPK inhibitors induces melanoma cells with resistance plasticity to inhibitors while retaining sensitivity to CD8 T cells

“…Redmer et al previously proposed that CD271 expression was essential for the tumorigenicity of CM cells (39). However, Cheli et al described CD271 as an imperfect CSC marker since only the slow growing cells among the CD271 + subpopulation presented increased tumorigenic potential (40). Our results support those of Ravindran Menon et al (41), who demonstrated that PLX4032 increased CD271 expression in CM cells and induced the transition into a slow cycling state.…”