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Heterogeneity and Plasticity of Breast Cancer Stem Cells

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Book cover Stem Cells Heterogeneity in Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1139))

Abstract

In the last 20 years, the conventional view of breast cancer as a homogeneous collection of highly proliferating malignant cells was totally replaced by a model of increased complexity, which points out that breast carcinomas are tissues composed of multiple populations of transformed cells. A large diversity of host cells and structural components of the extracellular matrix constitute the mammary tumour microenvironment, which supports its growth and progression, where individual cancer cells evolve with cumulative phenotypic and genetic heterogeneity. Moreover, contributing to this heterogeneity, it has been demonstrated that breast cancers can exhibit a hierarchical organization composed of tumour cells displaying divergent lineage biomarkers and where, at the apex of this hierarchy, some neoplastic cells are able to self-renew and to aberrantly differentiate. Breast cancer stem cells (BCSCs), as they were entitled, not only drive tumourigenesis, but also mediate metastasis and contribute to therapy resistance.

Recently, adding more complexity to the system, it has been demonstrated that BCSCs maintain high levels of plasticity, being able to change between mesenchymal-like and epithelial-like states in a process regulated by the tumour microenvironment. These stem cell state transitions play a fundamental role in the process of tumour metastasis, as well as in the resistance to putative therapeutic strategies to target these cells. In this chapter, it will be mainly discussed the emerging knowledge regarding the contribution of BCSCs to tumour heterogeneity, their plasticity, and the role that this plasticity can play in the establishment of distant metastasis. A major focus will also be given to potential clinical implications of these discoveries in breast cancer recurrence and to possible BCSC targeted therapeutics by the use of specific biomarkers.

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Acknowledgments

Acknowledgements should be given to FEDER—Fundo Europeu de Desenvolvimento Regional through the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by FCT- Fundação para a Ciência e a Tecnologia, under the project POCI-01-0145-FEDER-016390. IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274).

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Authors and Affiliations

  1. Institute of Pathology and Molecular Immunology of the University of Porto (Ipatimup), Porto, Portugal

    Bárbara Sousa, Ana Sofia Ribeiro & Joana Paredes

  2. Institute of Investigation and Innovation in Health (i3S), Porto, Portugal

    Bárbara Sousa, Ana Sofia Ribeiro & Joana Paredes

  3. Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal

    Joana Paredes

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  1. Bárbara Sousa
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  2. Ana Sofia Ribeiro
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  3. Joana Paredes
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Correspondence to Joana Paredes .

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  1. Department of Pathology, Federal University of Minas Gerais, Department of Radiology, Columbia University Medical Center, New York, NY, USA, Belo Horizonte, MG, Brazil

    Alexander Birbrair

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Sousa, B., Ribeiro, A.S., Paredes, J. (2019). Heterogeneity and Plasticity of Breast Cancer Stem Cells. In: Birbrair, A. (eds) Stem Cells Heterogeneity in Cancer. Advances in Experimental Medicine and Biology, vol 1139. Springer, Cham. https://doi.org/10.1007/978-3-030-14366-4_5

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