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Cancers (Basel). 2019 Aug 24;11(9). pii: E1240. doi: 10.3390/cancers11091240.

Role of the Microenvironment in Regulating Normal and Cancer Stem Cell Activity: Implications for Breast Cancer Progression and Therapy Response.

Bhat V1,2, Allan AL3,4, Raouf A5,6.

Author information

1
Department of Immunology, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada.
2
Research Institute in Oncology and Hematology, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada.
3
London Regional Cancer Program, London Health Science Centre, London, ON N6A 5W9, Canada.
4
Department of Anatomy & Cell Biology and Oncology, Western University, London, ON N6A 3K7, Canada.
5
Department of Immunology, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. afshin.raouf@umanitoba.ca.
6
Research Institute in Oncology and Hematology, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada. afshin.raouf@umanitoba.ca.

Abstract

The epithelial cells in an adult woman's breast tissue are continuously replaced throughout their reproductive life during pregnancy and estrus cycles. Such extensive epithelial cell turnover is governed by the primitive mammary stem cells (MaSCs) that proliferate and differentiate into bipotential and lineage-restricted progenitors that ultimately generate the mature breast epithelial cells. These cellular processes are orchestrated by tightly-regulated paracrine signals and crosstalk between breast epithelial cells and their tissue microenvironment. However, current evidence suggests that alterations to the communication between MaSCs, epithelial progenitors and their microenvironment plays an important role in breast carcinogenesis. In this article, we review the current knowledge regarding the role of the breast tissue microenvironment in regulating the special functions of normal and cancer stem cells. Understanding the crosstalk between MaSCs and their microenvironment will provide new insights into how an altered breast tissue microenvironment could contribute to breast cancer development, progression and therapy response and the implications of this for the development of novel therapeutic strategies to target cancer stem cells.

KEYWORDS:

breast cancer stem cells; cytokines; hypoxia; immune cells; mammary stem cells; microenvironment

PMID:
31450577
DOI:
10.3390/cancers11091240
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