CD133, Stem Cells, and Cancer Stem Cells: Myth or Reality?

Abstract

CD133, a member of the prominin family, is found in a variety of tissues with at least three variants. The function of CD133 is not well understood, but its expression is subject to changes in the microenvironment cues including bioenergetic stress. Knockout of CD133 does not affect renewal, but mammary gland branching. A point mutation of CD133 (R733C) leads to retinal disorder. CD133 is found in embryonic stem cells, normal tissue stem cells, stem cell niches, and circulating endothelial progenitors as well as cancer stem cells. Maintenance of stemness in cancer may be attributable to asymmetric cell division in association with a set of embryonic expression signatures in CD133+ tumor cells. CD133 could enrich cancer stem cells, which are associated with chemo- and radiation resistance phenotype. High CD133 is associated with poor survival in a variety of solid tumors, including lung, colon, prostate, etc. Monitoring CD133+ cells in peripheral blood, and targeting CD133 in cancer, may further predict and improve the clinical outcomes.

Fig. 1

A view of CD133 expression as it relates to variety of normal tissue and cancer stem cells. CD133 expression is due to the lack of CpG island methylation and is regulated by several important pathways, including miR-200a, which serves as stemness promoter through the canonical Wnt/β-catenin pathway. There are three reported isoforms, CD133-1, CD133-2, and CD133-3, which are detected in different tissue stem cells, niche, and normal tissues