Cancer stem cells in breast: current opinion and future challenges

Abstract

There is increasing evidence for the cancer stem cell hypothesis, which holds that cancers are driven by a cellular subcomponent that has stem cell properties, that is, self-renewal, tumorigenicity and multilineage differentiation capacity. The cancer stem cell hypothesis modifies our conceptual approach of oncogenesis and shall have implications in breast cancer prevention, detection and treatment, especially in metastatic breast cancer for which no curative treatment exists. Given the specific stem cell features, novel therapeutic pathways can be targeted. Following this approach, new molecules are currently in development. Focusing on the cross-talk between stem cells and their microenvironment is also a promising way to explore how to better target cancer stem cells and be curative.

Fig. 1

Purification and isolation techniques of breast CSC. a Side population technique in MCF7 cell line. Stem cells exclude Hoechst 33342 through their overexpression of transmembrane ATP-binding cassette molecules (upper graph). These cells do not exclude Hoechst in presence of verapamil, an ATP-binding cassette protein inhibitor (lower graph). b Tumorosphere technique in MCF7 cell line. Only stem cells are able to survive and proliferate in nonadherent and serum-free culture conditions. Stem cells from tumorospheres are enriched in stem and progenitor cells. c Immunosorting on CD44⁺ CD24^-/low lin^- phenotype. CSC are included in the rectangle. d ALDEFLUOR assay on a breast tumor. Stem cells need ALDH activity to initiate differentiation. The ALDEFLUOR technique allows to sort cells with high ALDH enzymatic activity adding a substrate of this enzyme (BAAA), metabolized in a green fluorescent product in ALDH1-positive cells (rectangle, upper graph). These cells do not metabolize the substrate in the presence of DEAB, an inhibitor of ALDH (lower graph).