A CD146 FACS Protocol Enriches for Luminal Keratin 14/19 Double Positive Human Breast Progenitors
| Autor: | Jiyoung Kim, Mikkel Morsing, Vera Timmermans-Wielenga, Lone Rønnov-Jessen, Agla J. Fridriksdottir, Ole W. Petersen, Ólöf Gerdur Ísberg, René Villadsen |
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| Přispěvatelé: | Biomedical Center (UI), Lífvísindasetur (HÍ), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland |
| Rok vydání: | 2019 |
| Předmět: |
Cell biology
Keratin 14 lcsh:Medicine Biology medicine.disease_cause Article Breast cancer Brjóstakrabbamein Krabbameinsrannsóknir Keratin medicine Progenitor cell lcsh:Science Stofnfrumurannsóknir Adult stem cells chemistry.chemical_classification Multidisciplinary lcsh:R Cancer medicine.disease Molecular biology Frumulíffræði chemistry CD146 lcsh:Q Stem cell Carcinogenesis Adult stem cell |
| Zdroj: | Ísberg, Ó G, Kim, J, Fridriksdottir, A J, Morsing, M, Timmermans-Wielenga, V, Rønnov-Jessen, L, Petersen, O W & Villadsen, R 2019, ' A CD146 FACS Protocol Enriches for Luminal Keratin 14/19 Double Positive Human Breast Progenitors ', Scientific Reports, vol. 9, 14843 . https://doi.org/10.1038/s41598-019-50903-9 Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Publisher's version (útgefin grein). Human breast cancer is believed to arise in luminal progenitors within the normal breast. A subset of these are double positive (DP) for basal and luminal keratins and localizes to a putative stem cell zone within ducts. We here present a new protocol based on a combination of CD146 with CD117 and CD326 which provides an up to thirty fold enrichment of the DP cells. We show by expression profiling, colony formation, and morphogenesis that CD146high/CD117high/CD326high DP cells belong to a luminal progenitor compartment. While these DP cells are located quite uniformly in ducts, with age a variant type of DP (vDP) cells, which is mainly CD146-negative, accumulates in lobules. Intriguingly, in specimens with BRCA1 mutations known to predispose for cancer, higher frequencies of lobular vDP cells are observed. We propose that vDP cells are strong candidates for tracing the cellular origin of breast cancer. We thank Lena Kristensen, Tove Marianne Lund and Anita Sharma Friismose for expert technical assistance. Benedikte Thuesen and Trine Foged Henriksen, Capio CFR Hospitaler are acknowledged for providing breast biopsy material. The Core Facility for Integrated Microscopy (University of Copenhagen) is acknowledged for confocal microscope accessibility. This work was supported by Novo Nordisk Fonden and Danish Research Council grant 10-092798 (to DanStem), Toyota-Fonden Denmark and Anita og Tage Therkelsens Fond (to R.V.), Familien Erichsens Mindefond and Vera og Carl Johan Michaelsens Legat (to J.K.), Harboefonden, Else og Mogens Wedell-wedellborgs Fond and Danish Cancer Society Grant R146-A9257 (to L.R.-J.). |
| Databáze: | OpenAIRE |
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