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A CD146 FACS Protocol Enriches for Luminal Keratin 14/19 Double Positive Human Breast Progenitors

Gerdur Ísberg, Ólöf ; Kim, Jiyoung ; Fridriksdottir, Agla J. ; Morsing, Mikkel LU ; Timmermans-Wielenga, Vera ; Rønnov-Jessen, Lone ; Petersen, Ole W. and Villadsen, René (2019) In Scientific Reports 9(1).
Abstract

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... (More)

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.

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; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
9
issue
1
article number
14843
publisher
Nature Publishing Group
external identifiers
  • pmid:31619692
  • scopus:85073435779
ISSN
2045-2322
DOI
10.1038/s41598-019-50903-9
language
English
LU publication?
yes
id
e2018cf5-8a57-4098-bcaf-43b9bdb9b223
date added to LUP
2019-10-28 11:05:35
date last changed
2021-04-06 05:45:04
@article{e2018cf5-8a57-4098-bcaf-43b9bdb9b223,
  abstract     = {<p>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 CD146<sup>high</sup>/CD117<sup>high</sup>/CD326<sup>high</sup> 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.</p>},
  author       = {Gerdur Ísberg, Ólöf and Kim, Jiyoung and Fridriksdottir, Agla J. and Morsing, Mikkel and Timmermans-Wielenga, Vera and Rønnov-Jessen, Lone and Petersen, Ole W. and Villadsen, René},
  issn         = {2045-2322},
  language     = {eng},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {A CD146 FACS Protocol Enriches for Luminal Keratin 14/19 Double Positive Human Breast Progenitors},
  url          = {http://dx.doi.org/10.1038/s41598-019-50903-9},
  doi          = {10.1038/s41598-019-50903-9},
  volume       = {9},
  year         = {2019},
}