Abstract

Objectives:CD133 is considered a cancer stem cell (CSC) marker in various malignancies; however, its role as a biomarker of malignant melanoma remains controversial. The present study was conducted to evaluate the suitability of CD133 surface antigen as a CSC marker in melanoma. Methods:Human melanoma cells were fractionally separated by magnetic cell separation depending on the CD133 phenotype and transplanted into immunodeficient mice to evaluate their tumorigenic capacity. Furthermore, the time until the development of a palpable tumor and the growth rate were measured, and the final tumor volume was assessed after 8 weeks. The immunohistochemical expression of CD133 in the induced neoplasia was then compared using histomorphometry. Results:Notably, neoplasms were induced in all the groups (n = 48), including in the CD133-negative group. Tumors induced by unsorted cells had the largest volume (p = 0.014) but were detected significantly later in this group (p ≤ 0.001). Interestingly, all explanted tumors expressed CD133, with no significant differences among groups. Conclusions:In contrast to the results obtained in prior studies, the suitability of CD133 as a CSC marker could not be demonstrated. The current encouraging progress in targeted therapy for malignant melanoma highlights the need to identify more effective targets.

Highlights

  • Despite major therapeutic advances and the development of new treatment options, cutaneous melanoma continues to have the highest mortality rate among skin tumors (Cronin et al, 2018; Schvartsman et al, 2019)

  • The present study was conducted to evaluate the suitability of CD133 surface antigen as a cancer stem cell (CSC) marker in melanoma

  • Phenotypic characterization As a first step, phenotypic characterization of D10 cells according to CD133 epitope expression was performed by flow cytometry; it was determined that 10.7% of these cells were positive for CD133 (CD133pos cells)

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Summary

Introduction

Despite major therapeutic advances and the development of new treatment options, cutaneous melanoma continues to have the highest mortality rate among skin tumors (Cronin et al, 2018; Schvartsman et al, 2019). The exact physiological function of CD133 remains to be elucidated and its natural ligand is unknown, it appears to be involved in cell differentiation and signal transduction (Sun et al, 2012; Bauer et al, 2011; Irollo and Pirozzi, 2013). This cell-surface protein is regarded as an important driver of tumor progression and as a putative cancer stem cell (CSC) marker (Glumac and LeBeau, 2018).

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