Dynamic regulation of CD24 and the invasive, CD44posCD24negphenotype in breast cancer cell lines

Abstract

Introduction: The invasive, mesenchymal phenotype of CD44posCD24negbreast cancer cells has made them a promising target for eliminating the metastatic capacity of primary tumors. It has been previously demonstrated that CD44neg/lowCD24posbreast cancer cells lack the ability to give rise to their invasive CD44posCD24negcounterpart. Here we demonstrate that noninvasive, epithelial-like CD44posCD24poscells readily give rise to invasive, mesenchymal CD44posCD24negprogeny in vivo and in vitro. This interconversion was found to be dependent upon Activin/Nodal signaling.Methods: Breast cancer cell lines were sorted into CD44posCD24posand CD44posCD24negpopulations to evaluate their progeny for the expression of CD44, CD24, and markers of a mesenchymal phenotype. The populations, separated by fluorescence activated cell sorting (FACS) were injected into immunocompromised mice to evaluate their tumorigenicity and invasiveness of the resulting xenografts.Results: CD24 expression was dynamically regulated in vitro in all evaluated breast cancer cell lines. Furthermore, a single noninvasive, epithelial-like CD44posCD24poscell had the ability to give rise to invasive, mesenchymal CD44posCD24negprogeny. Importantly, this interconversion occurred in vivo as CD44posCD24poscells gave rise to xenografts with locally invasive borders as seen in xenografts initiated with CD44posCD24negcells. Lastly, the ability of CD44posCD24poscells to give rise to mesenchymal progeny, and vice versa, was blocked upon ablation of Activin/Nodal signaling.Conclusions: Our data demonstrate that the invasive, mesenchymal CD44posCD24negphenotype is under dynamic control in breast cancer cell lines both in vitro and in vivo. Furthermore, our observations suggest that therapies targeting CD44posCD24negtumor cells may have limited success in preventing primary tumor metastasis unless Activin/Nodal signaling is arrested. © 2009 Meyer et al.; licensee BioMed Central Ltd.