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Title: Parity reduces mammary repopulating activity but does not affect mammary stem cells defined as CD24 + CD29/CD49fhi in mice.
Austin Authors: Dall, Genevieve V;Vieusseux, Jessica;Seyed-Razavi, Yashar;Godde, Nathan;Ludford-Menting, Mandy;Russell, Sarah M;Ashworth, Alan;Anderson, Robin L ;Risbridger, Gail P;Shackleton, Mark;Britt, Kara L
Affiliation: Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA, USA
Immune Signaling Laboratory, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, VIC, Australia
The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia
Pathology and Pathogenesis Group, CSIRO Australian Animal Health Laboratory, Geelong, VIC, Australia
Breast Cancer Risk and Prevention Laboratory, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, VIC, Australia
School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia
Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, Australia
Cancer Development and Treatment, Alfred Hospital, Monash University, Melbourne, VIC, Australia
Metastasis Research Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Centre for Micro-Photonics, Swinburne University, Hawthorn, VIC, Australia
Issue Date: Oct-2020
Date: 2020-07-21
Publication information: Breast cancer research and treatment 2020; 183(3): 565-575
Abstract: Breast cancer (BCa) mortality is decreasing with early detection and improvement in therapies. The incidence of BCa, however, continues to increase, particularly estrogen-receptor-positive (ER +) subtypes. One of the greatest modifiers of ER + BCa risk is childbearing (parity), with BCa risk halved in young multiparous mothers. Despite convincing epidemiological data, the biology that underpins this protection remains unclear. Parity-induced protection has been postulated to be due to a decrease in mammary stem cells (MaSCs); however, reports to date have provided conflicting data. We have completed rigorous functional testing of repopulating activity in parous mice using unfractionated and MaSC (CD24midCD49fhi)-enriched populations. We also developed a novel serial transplant method to enable us to assess self-renewal of MaSC following pregnancy. Lastly, as each pregnancy confers additional BCa protection, we subjected mice to multiple rounds of pregnancy to assess whether additional pregnancies impact MaSC activity. Here, we report that while repopulating activity in the mammary gland is reduced by parity in the unfractionated gland, it is not due to a loss in the classically defined MaSC (CD24+CD49fhi) numbers or function. Self-renewal was unaffected by parity and additional rounds of pregnancy also did not lead to a decrease in MaSC activity. Our data show instead that parity impacts on the stem-like activity of cells outside the MaSC population.
DOI: 10.1007/s10549-020-05804-1
ORCID: 0000-0001-6069-7856
Journal: Breast cancer research and treatment
PubMed URL: 32696317
Type: Journal Article
Subjects: Breast cancer
Mammary fat pad transplants
Stem cells
Appears in Collections:Journal articles

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