CXCR6, a Newly Defined Biomarker of Tissue-Specific Stem Cell Asymmetric Self-Renewal, Identifies More Aggressive Human Melanoma Cancer Stem Cells

TL;DR

This study identifies CXCR6 as a biomarker for tissue-specific stem cell-like cancer stem cells in melanoma, revealing that more aggressive tumor cells retain asymmetric self-renewal properties, which could inform new therapeutic strategies.

Contribution

It provides the first phenotypic evidence linking melanoma CSCs to mutated tissue-specific stem cells and identifies CXCR6+ cells as a more aggressive subpopulation.

Findings

CXCR6+ cells are more aggressive melanoma CSCs

Asymmetric self-renewal correlates with tumor aggressiveness

Tumor progression involves retention of tissue-specific stem cell traits

Abstract

Background: A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs) from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+. Conclusions/Significance: The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.