nach oben

Erschienen in:

21.07.2020 | Preclinical study

Parity reduces mammary repopulating activity but does not affect mammary stem cells defined as CD24 + CD29/CD49fhi in mice

verfasst von: Genevieve V. Dall, Jessica Vieusseux, Yashar Seyed-Razavi, Nathan Godde, Mandy Ludford-Menting, Sarah M. Russell, Alan Ashworth, Robin L. Anderson, Gail P. Risbridger, Mark Shackleton, Kara L. Britt

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

Abstract

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 (CD24^midCD49f^hi)-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⁺CD49f^hi) 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.

Nur mit Berechtigung zugänglich

Bigaard J et al (2012) Breast cancer incidence by estrogen receptor status in Denmark from 1996 to 2007. Breast Cancer Res Treat 136(2):559–564PubMed

Glass AG, Hoover RN (1990) Rising incidence of breast cancer: relationship to stage and receptor status. J Natl Cancer Inst 82(8):693–696PubMed

Li CI, Daling JR, Malone KE (2003) Incidence of invasive breast cancer by hormone receptor status from 1992 to 1998. J Clin Oncol 21(1):28–34PubMed

Rosenberg PS, Barker KA, Anderson WF (2015) Estrogen Receptor status and the future burden of invasive and in situ breast cancers in the United States. J Natl Cancer Inst 107(9):djv159PubMedPubMedCentral

Howalder N et al (2016) SEER cancer statistics review, 1975–2013. National Cancer Institute, Bethesda, MD

Youlden DR et al (2014) Incidence and mortality of female breast cancer in the Asia-Pacific region. Cancer Biol Med 11(2):101–115PubMedPubMedCentral

AIHW (2012) Breast Cancer in Australia: an overview in Cancer Series no 71 Cat no CAN67. Australian Institute of Health and Welfare and National Breast and Ovarian Cancer Centre, Canberra

Dall GV, Britt KL (2017) Estrogen effects on the mammary gland in early and late life and breast cancer risk. Front Oncol 7:110PubMedPubMedCentral

Collaborative Group on Hormonal Factors in Breast, C (2012) Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol 13(11):1141–1151

10.

Collaborative Group on Hormonal Factors in Breast, C (2002) Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries. Lancet 360:187–195

11.

MacMahon B et al (1970) Age at first birth and breast cancer risk. Bull World Health Organ 43(2):209–221PubMedPubMedCentral

12.

Ewertz M et al (1990) Age at first birth, parity and risk of breast cancer: a meta-analysis of 8 studies from the Nordic countries. Int J Cancer 46(4):597–603PubMed

13.

Britt K, Ashworth A, Smalley M (2007) Pregnancy and the risk of breast cancer. Endocr Relat Cancer 14(4):907–933PubMed

14.

Chang CC et al (2001) A human breast epithelial cell type with stem cell characteristics as target cells for carcinogenesis. Radiat Res 155(1 Pt 2):201–207PubMed

15.

Russo J, Tay LK, Russo IH (1982) Differentiation of the mammary gland and susceptibility to carcinogenesis. Breast Cancer Res Treat 2(1):5–73PubMed

16.

Russo J, Russo IH (1978) DNA labeling index and structure of the rat mammary gland as determinants of its susceptibility to carcinogenesis. J Natl Cancer Inst 61(6):1451–1459PubMed

17.

Tokunaga M et al (1994) Incidence of female breast cancer among atomic bomb survivors, 1950–1985. Radiat Res 138(2):209–223PubMed

18.

Land CE et al (2003) Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950–1990. Radiat Res 160(6):707–717PubMed

19.

Siwko SK et al (2008) Evidence that an early pregnancy causes a persistent decrease in the number of functional mammary epithelial stem cells–implications for pregnancy-induced protection against breast cancer. Stem Cells 26(12):3205–3209PubMedPubMedCentral

20.

Meier-Abt F et al (2013) Parity induces differentiation and reduces Wnt/Notch signaling ratio and proliferation potential of basal stem/progenitor cells isolated from mouse mammary epithelium. Breast Cancer Res 15(2):R36PubMedPubMedCentral

21.

Britt KL et al (2009) Pregnancy in the mature adult mouse does not alter the proportion of mammary epithelial stem/progenitor cells. Breast Cancer Res 11(2):R20PubMedPubMedCentral

22.

Vaillant F, Lindeman GJ, Visvader JE (2011) Jekyll or Hyde: does Matrigel provide a more or less physiological environment in mammary repopulating assays? Breast Cancer Res 13(3):108PubMedPubMedCentral

23.

Gupta PB et al (2007) Systemic stromal effects of estrogen promote the growth of estrogen receptor-negative cancers. Cancer Res 67(5):2062–2071PubMed

24.

Schedin P (2006) Pregnancy-associated breast cancer and metastasis. Nat Rev Cancer 6(4):281–291PubMed

25.

Tikoo A et al (2012) Physiological levels of Pik3ca(H1047R) mutation in the mouse mammary gland results in ductal hyperplasia and formation of ERalpha-positive tumors. PLoS ONE 7(5):e36924PubMedPubMedCentral

26.

Flurkey, C.a.H., The mouse in Biomedical Research, ed. J. Fox. 2007: American College of Laboratory Animal Medicine (Elsevier).

27.

Lilla JN et al (2009) Active plasma kallikrein localizes to mast cells and regulates epithelial cell apoptosis, adipocyte differentiation, and stromal remodeling during mammary gland involution. J Biol Chem 284(20):13792–13803PubMedPubMedCentral

28.

Sleeman KE et al (2006) CD24 staining of mouse mammary gland cells defines luminal epithelial, myoepithelial/basal and non-epithelial cells. Breast Cancer Res 8(1):R7PubMed

29.

Sleeman KE et al (2007) Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland. J Cell Biol 176(1):19–26PubMedPubMedCentral

30.

Dall GV et al (2017) SCA-1 Labels a subset of estrogen-responsive bipotential repopulating cells within the CD24+ CD49fhi mammary stem cell-enriched compartment. Stem Cell Rep 8(2):417–431

31.

Hu Y, Smyth GK (2009) ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays. J Immunol Methods 347(1–2):70–78PubMed

32.

Dall G, Risbridger G, Britt K (2016) Mammary stem cells and parity-induced breast cancer protection- new insights. J Steroid Biochem Mol Biol 170:54–60PubMed

33.

Shackleton M et al (2006) Generation of a functional mammary gland from a single stem cell. Nature 439(7072):84–88PubMed

34.

Stingl J et al (2006) Purification and unique properties of mammary epithelial stem cells. Nature 439(7079):993–997PubMed

35.

Prater MD et al (2014) Mammary stem cells have myoepithelial cell properties. Nat Cell Biol 16(10):942–950PubMedPubMedCentral

36.

Tamakoshi K et al (2005) Impact of menstrual and reproductive factors on breast cancer risk in Japan: results of the JACC study. Cancer Sci 96(1):57–62PubMed

37.

Suh JS et al (1996) Menstrual and reproductive factors related to the risk of breast cancer in Korea. Ovarian hormone effect on breast cancer. J Korean Med Sci 11(6):501–508PubMedPubMedCentral

38.

Kato I et al (1992) A case-control study of breast cancer among Japanese women: with special reference to family history and reproductive and dietary factors. Breast Cancer Res Treat 24(1):51–59PubMed

39.

Hirose K et al (1995) A large-scale, hospital-based case-control study of risk factors of breast cancer according to menopausal status. Jpn J Cancer Res 86(2):146–154PubMedPubMedCentral

40.

Russo J, Wilgus G, Russo IH (1979) Susceptibility of the mammary gland to carcinogenesis: I Differentiation of the mammary gland as determinant of tumor incidence and type of lesion. Am J Pathol 96(3):721–736PubMedPubMedCentral

41.

Russo IH, Russo J (1978) Developmental stage of the rat mammary gland as determinant of its susceptibility to 7,12-dimethylbenz[a]anthracene. J Natl Cancer Inst 61(6):1439–1449PubMed

42.

Boice JD Jr et al (1991) Frequent chest X-ray fluoroscopy and breast cancer incidence among tuberculosis patients in Massachusetts. Radiat Res 125(2):214–222PubMed

43.

Cohn BA et al (2007) DDT and breast cancer in young women: new data on the significance of age at exposure. Environ Health Perspect 115(10):1406–1414PubMedPubMedCentral

44.

Hoffman DA et al (1989) Breast cancer in women with scoliosis exposed to multiple diagnostic x rays. J Natl Cancer Inst 81(17):1307–1312PubMed

45.

McGregor H et al (1977) Breast cancer incidence among atomic bomb survivors, Hiroshima and Nagasaki, 1950–69. J Natl Cancer Inst 59(3):799–811PubMed

46.

Albrektsen G et al (2005) Breast cancer risk by age at birth, time since birth and time intervals between births: exploring interaction effects. Br J Cancer 92(1):167–175PubMed

47.

Press DJ, Pharoah P (2010) Risk factors for breast cancer: a reanalysis of two case-control studies from 1926 and 1931. Epidemiology 21(4):566–572PubMed

48.

Ursin G et al (2005) Reproductive factors and subtypes of breast cancer defined by hormone receptor and histology. Br J Cancer 93(3):364–371PubMedPubMedCentral

49.

van Amerongen R, Bowman AN, Nusse R (2012) Developmental stage and time dictate the fate of Wnt/beta-catenin-responsive stem cells in the mammary gland. Cell Stem Cell 11(3):387–400PubMed

50.

Rios AC et al (2014) In situ identification of bipotent stem cells in the mammary gland. Nature 506(7488):322–327PubMed

51.

Woodward WA et al (2007) WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc Natl Acad Sci U S A 104(2):618–623PubMedPubMedCentral

52.

Insinga A et al (2013) DNA damage in stem cells activates p21, inhibits p53, and induces symmetric self-renewing divisions. Proc Natl Acad Sci U S A 110(10):3931–3936PubMedPubMedCentral

53.

Huh SJ et al (2015) Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells. Stem Cell Rep 4(2):297–311

54.

Plaks V et al (2013) Lgr5-expressing cells are sufficient and necessary for postnatal mammary gland organogenesis. Cell Rep 3(1):70–78PubMedPubMedCentral

55.

Lim E et al (2010) Transcriptome analyses of mouse and human mammary cell subpopulations reveal multiple conserved genes and pathways. Breast Cancer Res 12(2):R21PubMedPubMedCentral

56.

Shehata M et al (2012) Phenotypic and functional characterisation of the luminal cell hierarchy of the mammary gland. Breast Cancer Res 14(5):R134PubMedPubMedCentral

Titel: Parity reduces mammary repopulating activity but does not affect mammary stem cells defined as CD24 + CD29/CD49fhi in mice
verfasst von: Genevieve V. Dall
Jessica Vieusseux
Yashar Seyed-Razavi
Nathan Godde
Mandy Ludford-Menting
Sarah M. Russell
Alan Ashworth
Robin L. Anderson
Gail P. Risbridger
Mark Shackleton
Kara L. Britt
Publikationsdatum: 21.07.2020
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2020
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05804-1

Neu im Fachgebiet Onkologie

18.04.2024 | Wirbelsäulenmetastase | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Parity reduces mammary repopulating activity but does not affect mammary stem cells defined as CD24 + CD29/CD49fhi in mice

Abstract

Background

Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Adjuvante Brustkrebstherapie: Doppelt hält besser

HNO-Op. auch mit über 90?

Manche Gestagene können das Risiko für Meningeome erhöhen

Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2020

A system for risk stratification and prioritization of breast cancer surgeries delayed by the COVID-19 pandemic: preparing for re-entry

Identifying germline APOBEC3B deletion and immune phenotype in Korean patients with operable breast cancer

The histopathological and molecular features of breast carcinoma with tumour budding—a systematic review and meta-analysis

Sarcoma of the breast: breast cancer history as etiologic and prognostic factor—A population-based case–control study

Pre-operative axillary ultrasound with fine-needle aspiration cytology performance and predictive factors of false negatives in axillary lymph node involvement in early breast cancer

The efficacy of first-line chemotherapy in endocrine-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer

Neu im Fachgebiet Onkologie

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Adjuvante Brustkrebstherapie: Doppelt hält besser

HNO-Op. auch mit über 90?

Manche Gestagene können das Risiko für Meningeome erhöhen

Update Onkologie