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 Resjournal_title
Cell researchauthors
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 YAdoi
10.1038/s41422-019-0225-9subject
Has Abstractpub_date
2019-10-01 00:00:00pages
832-845issue
10eissn
1001-0602issn
1748-7838pii
10.1038/s41422-019-0225-9journal_volume
29pub_type
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