Protein C receptor is a therapeutic stem cell target in a distinct group of breast cancers.

Abstract:

:Breast cancer is a heterogeneous disease. In particular, triple-negative breast cancer (TNBC) comprises various molecular subgroups with unclear identities and currently has few targeted treatment options. Our previous study identified protein C receptor (Procr) as a surface marker on mammary stem cells (MaSCs) located in the basal layer of the normal mammary gland. Given the possible connection of TNBC with basal layer stem cells, we conducted comparative analyses of Procr in breast cancers of mouse and human origin. In mouse mammary tumors, we showed that Procr+ cells are enriched for cancer stem cells (CSCs) in Wnt1 basal-like tumors, but not in Brca1 basal-like tumors or PyVT luminal tumors. In human cancers, PROCR was robustly expressed in half of TNBC cases. Experiments with patient-derived xenografts (PDXs) revealed that PROCR marks CSCs in this discrete subgroup (referred to as PROCR+ TNBC). Interfering with the function of PROCR using an inhibitory nanobody reduced the CSC numbers, arrested tumor growth and prevented rapid tumor recurrence. Our data suggest a key role of MaSC in breast tumorigenesis. Moreover, our work indicates that PROCR can be used as a biomarker to stratify TNBC into clinically relevant subgroups and may provide a novel targeted treatment strategy for this clinically important tumor subtype.

journal_name

Cell Res

journal_title

Cell research

authors

Wang D,Hu X,Liu C,Jia Y,Bai Y,Cai C,Wang J,Bai L,Yang R,Lin C,Liu YR,Li S,Qiao F,Yao L,Chen L,Ge G,Jiang H,Li D,Li L,Chen J,Shao ZM,Zeng YA

doi

10.1038/s41422-019-0225-9

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

832-845

issue

10

eissn

1001-0602

issn

1748-7838

pii

10.1038/s41422-019-0225-9

journal_volume

29

pub_type

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