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

Ólöf Gerdur Ísberg; Jiyoung Kim; Agla J. Fridriksdottir; Mikkel Morsing; Vera Timmermans-Wielenga; Lone Rønnov-Jessen; Ole W. Petersen; René Villadsen

doi:10.1038/s41598-019-50903-9

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

Ólöf Gerdur Ísberg, Jiyoung Kim, Agla J. Fridriksdottir, Mikkel Morsing, Vera Timmermans-Wielenga, Lone Rønnov-Jessen, Ole W. Petersen, René Villadsen

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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 CD146^high/CD117^high/CD326^high 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.

Originalsprog	Engelsk
Artikelnummer	14843
Tidsskrift	Scientific Reports
Vol/bind	9
Antal sider	11
ISSN	2045-2322
DOI	https://doi.org/10.1038/s41598-019-50903-9
Status	Udgivet - 1 dec. 2019

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10.1038/s41598-019-50903-9Licens: CC BY

A CD146 FACS Protocol Enriches for Luminal Keratin 1419 Double Positive Human Breast ProgenitorsForlagets udgivne version, 4,15 MBLicens: CC BY

Citationsformater

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

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 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.",

author = "{\'I}sberg, {{\'O}l{\"o}f Gerdur} and Jiyoung Kim and Fridriksdottir, {Agla J.} and Mikkel Morsing and Vera Timmermans-Wielenga and Lone R{\o}nnov-Jessen and Petersen, {Ole W.} and Ren{\'e} Villadsen",

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T1 - A CD146 FACS Protocol Enriches for Luminal Keratin 14/19 Double Positive Human Breast Progenitors

AU - Ísberg, Ólöf Gerdur

AU - Kim, Jiyoung

AU - Fridriksdottir, Agla J.

AU - Morsing, Mikkel

AU - Timmermans-Wielenga, Vera

AU - Rønnov-Jessen, Lone

AU - Petersen, Ole W.

AU - Villadsen, René

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-019-50903-9

DO - 10.1038/s41598-019-50903-9

M3 - Journal article

C2 - 31619692

SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

M1 - 14843

ER -

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

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