Parity reduces mammary repopulating activity but does not affect mammary stem cells defined as CD24 + CD29/CD49fhi in mice
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Our data show instead that parity impacts on the stem-like activity of cells outside the MaSC population.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:183 |
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| Enthalten in: |
Breast cancer research and treatment - 183(2020), 3 vom: 16. Okt., Seite 565-575 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dall, Genevieve V [VerfasserIn] |
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| Links: |
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| Themen: |
Breast cancer |
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| Anmerkungen: |
Date Completed 23.06.2021 Date Revised 23.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s10549-020-05804-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM312725027 |
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| 245 | 1 | 0 | |a Parity reduces mammary repopulating activity but does not affect mammary stem cells defined as CD24 + CD29/CD49fhi in mice |
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| 500 | |a Date Revised 23.06.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: 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 | ||
| 520 | |a METHODS: 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 | ||
| 520 | |a RESULTS: 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 | ||
| 520 | |a CONCLUSIONS: Our data show instead that parity impacts on the stem-like activity of cells outside the MaSC population | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Breast cancer | |
| 650 | 4 | |a Mammary fat pad transplants | |
| 650 | 4 | |a Parity | |
| 650 | 4 | |a Stem cells | |
| 650 | 7 | |a Integrin beta1 |2 NLM | |
| 700 | 1 | |a Vieusseux, Jessica |e verfasserin |4 aut | |
| 700 | 1 | |a Seyed-Razavi, Yashar |e verfasserin |4 aut | |
| 700 | 1 | |a Godde, Nathan |e verfasserin |4 aut | |
| 700 | 1 | |a Ludford-Menting, Mandy |e verfasserin |4 aut | |
| 700 | 1 | |a Russell, Sarah M |e verfasserin |4 aut | |
| 700 | 1 | |a Ashworth, Alan |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Robin L |e verfasserin |4 aut | |
| 700 | 1 | |a Risbridger, Gail P |e verfasserin |4 aut | |
| 700 | 1 | |a Shackleton, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Britt, Kara L |e verfasserin |4 aut | |
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