Nerve Growth Factor and proNGF Simultaneously Promote Symmetric Self‐Renewal, Quiescence, and Epithelial to Mesenchymal Transition to Enlarge the Breast Cancer Stem Cell Compartment. (22nd January 2015)

• Record Type: Journal Article
• Authors: Tomellini, Elisa; Touil, Yasmine; Lagadec, Chann; Julien, Sylvain; Ostyn, Pauline; Ziental‐Gelus, Nathalie; Meignan, Samuel; Lengrand, Justine; Adriaenssens, Eric; Polakowska, Renata; Le Bourhis, Xuefen
• Is Part Of: Stem cells. Volume 33:Number 2(2015:Feb.)
• Page Start: 342
• Page End: 353
• Publication Date: 2015-01-22
• Subjects: Nerve growth factor -- proNGF -- p75NTR -- Breast cancer stem cells; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1849
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: The discovery of cancer stem cells (CSCs) fundamentally advanced our understanding of the mechanisms governing breast cancer development. However, the stimuli that control breast CSC self‐renewal and differentiation have still not been fully detailed. We previously showed that nerve growth factor (NGF) and its precursor proNGF can stimulate breast cancer cell growth and invasion in an autocrine manner. In this study, we investigated the effects of NGF and proNGF on the breast CSC compartment and found that NGF or proNGF enrich for CSCs in several breast cancer cell lines. This enrichment appeared to be achieved by increasing the number of symmetric divisions of quiescent/slow‐proliferating CSCs. Interestingly, in vitro NGF pretreatment of MCF‐7 luminal breast cancer cells promoted epithelial to mesenchymal transition in tumors of severe combined immunodeficient mice. Furthermore, p75 NTR, the common receptor for both neurotrophins and proneurotrophins, mediated breast CSC self‐renewal by regulating the expression of pluripotency transcription factors. Our data indicate, for the first time, that the NGF/proNGF/p75 NTR axis plays a critical role in regulating breast CSC self‐renewal and plasticity. Stem Cells 2015;33:342–353