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Crit Rev Oncol Hematol. 2017 May;113:111-121. doi: 10.1016/j.critrevonc.2017.03.016. Epub 2017 Mar 16.

The cancer stem cell phenotype as a determinant factor of the heterotypic nature of breast tumors.

Author information

1
CNC - Center for Neurosciences and Cell Biology, University of Coimbra, Faculty of Medicine (Polo 1), Rua Larga, 3004-504 Coimbra, Portugal. Electronic address: nuno.fonseca@cnc.uc.pt.
2
CNC - Center for Neurosciences and Cell Biology, University of Coimbra, Faculty of Medicine (Polo 1), Rua Larga, 3004-504 Coimbra, Portugal; FFUC - Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. Electronic address: anafilipafcruz@gmail.com.
3
CNC - Center for Neurosciences and Cell Biology, University of Coimbra, Faculty of Medicine (Polo 1), Rua Larga, 3004-504 Coimbra, Portugal; TREAT U, SA - Parque Industrial de Taveiro, Lote 44, 3045-508 Coimbra, Portugal. Electronic address: vera.moura@treatu.pt.
4
CNC - Center for Neurosciences and Cell Biology, University of Coimbra, Faculty of Medicine (Polo 1), Rua Larga, 3004-504 Coimbra, Portugal; FFUC - Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. Electronic address: ssimoes@ci.uc.pt.
5
CNC - Center for Neurosciences and Cell Biology, University of Coimbra, Faculty of Medicine (Polo 1), Rua Larga, 3004-504 Coimbra, Portugal; FFUC - Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. Electronic address: jmoreira@ff.uc.pt.

Abstract

Gathering evidence supports the existence of a population of cells with stem-like characteristics, named cancer stem cells (CSC), which is involved not only in tumor recurrence but also in tumorigenicity, metastization and drug resistance. Several markers have been used to identify putative CSC sub-populations in different cancers. Notwithstanding, it has been acknowledged that breast CSC may originate from non-stem cancer cells (non-SCC), interconverting through an epithelial-to-mesenchymal transition-mediated process, and presenting several deregulated canonical and developmental signaling pathways. These support the heterogeneity that, directly or indirectly, influences fundamental biological features supporting breast tumor development. Accordingly, CSC have increasingly become highly relevant cellular targets. In this review, we will address the stemness concept in cancer, setting the perspective on CSC and their origin, by exploring their relation and regulation within the tumor microenvironment, in the context of emerging therapeutic targets. Within this framework, we will discuss nucleolin, a protein that has been associated with angiogenesis and, more recently, with the stemness phenotype, becoming a common denominator between CSC and non-SCC for multicellular targeting.

KEYWORDS:

Breast cancer; Cancer stem cells; Nucleolin; Tumor microenvironment

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