Dynamic regulation of CD24 and the invasive, CD44posCD24negphenotype in breast cancer cell linesReportar como inadecuado




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Breast Cancer Research

, 11:R82

First Online: 11 November 2009Received: 04 August 2009Revised: 21 October 2009Accepted: 11 November 2009

Abstract

IntroductionThe invasive, mesenchymal phenotype of CD44CD24 breast cancer cells has made them a promising target for eliminating the metastatic capacity of primary tumors. It has been previously demonstrated that CD44CD24 breast cancer cells lack the ability to give rise to their invasive CD44CD24 counterpart. Here we demonstrate that noninvasive, epithelial-like CD44CD24 cells readily give rise to invasive, mesenchymal CD44CD24 progeny in vivo and in vitro. This interconversion was found to be dependent upon Activin-Nodal signaling.

MethodsBreast cancer cell lines were sorted into CD44CD24 and CD44CD24 populations 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.

ResultsCD24 expression was dynamically regulated in vitro in all evaluated breast cancer cell lines. Furthermore, a single noninvasive, epithelial-like CD44CD24 cell had the ability to give rise to invasive, mesenchymal CD44CD24 progeny. Importantly, this interconversion occurred in vivo as CD44CD24 cells gave rise to xenografts with locally invasive borders as seen in xenografts initiated with CD44CD24 cells. Lastly, the ability of CD44CD24 cells to give rise to mesenchymal progeny, and vice versa, was blocked upon ablation of Activin-Nodal signaling.

ConclusionsOur data demonstrate that the invasive, mesenchymal CD44CD24 phenotype is under dynamic control in breast cancer cell lines both in vitro and in vivo. Furthermore, our observations suggest that therapies targeting CD44CD24 tumor cells may have limited success in preventing primary tumor metastasis unless Activin-Nodal signaling is arrested.

Abbreviations7AAD7-aminoactinomycin D

APCallophycocyanin

E-cadE-cadherin

FACSfluorescence activated cell sorting

FBSfetal bovine calf serum

FITCfluorescein

negnegative

PEphycoerythrin

pospositive

Electronic supplementary materialThe online version of this article doi:10.1186-bcr2449 contains supplementary material, which is available to authorized users.

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Autor: Matthew J Meyer - Jodie M Fleming - Mustapha A Ali - Mitchell W Pesesky - Erika Ginsburg - Barbara K Vonderhaar

Fuente: https://link.springer.com/



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