Open Access∆Np63/p40 correlates with the location and phenotype of basal/mesenchymal cancer stem‐like cells in human ER + and HER2 + breast cancers
Author(s) -
Liu Yajing,
Nekulova Marta,
Nenutil Rudolf,
Horakova Iva,
Appleyard M Virginia,
Murray Karen,
Holcakova Jitka,
Galoczova Michaela,
Quinlan Philip,
Jordan Lee B,
Purdie Colin A,
Vojtesek Borivoj,
Thompson Alastair M,
Coates Philip J
Publication year - 2020
Publication title -
the journal of pathology: clinical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.849
H-Index - 21
ISSN - 2056-4538
DOI - 10.1002/cjp2.149
Subject(s) - cd44 , cancer stem cell , cancer research , population , stem cell , biology , pathology , breast cancer , cancer cell , cancer , cell , medicine , microbiology and biotechnology , genetics , environmental health
ΔNp63, also known as p40, regulates stemness of normal mammary gland epithelium and provides stem cell characteristics in basal and HER2‐driven murine breast cancer models. Whilst ΔNp63/p40 is a characteristic feature of normal basal cells and basal‐type triple‐negative breast cancer, some receptor‐positive breast cancers express ΔNp63/p40 and its overexpression imparts cancer stem cell‐like properties in ER + cell lines. However, the incidence of ER + and HER2 + tumours that express ΔNp63/p40 is unclear and the phenotype of ΔNp63/p40 + cells in these tumours remains uncertain. Using immunohistochemistry with p63 isoform‐specific antibodies, we identified a ΔNp63/p40 + tumour cell subpopulation in 100 of 173 (58%) non‐triple negative breast cancers and the presence of this population associated with improved survival in patients with ER − /HER2 + tumours ( p = 0.006). Furthermore, 41% of ER + /PR + and/or HER2 + locally metastatic breast cancers expressed ΔNp63/p40, and these cells commonly accounted for <1% of the metastatic tumour cell population that localised to the tumour/stroma interface, exhibited an undifferentiated phenotype and were CD44 + /ALDH − . In vitro studies revealed that MCF7 and T47D (ER + ) and BT‐474 (HER2 + ) breast cancer cell lines similarly contained a small subpopulation of ΔNp63/p40 + cells that increased in mammospheres. In vivo , MCF7 xenografts contained ΔNp63/p40 + cells with a similar phenotype to primary ER + cancers. Consistent with tumour samples, these cells also showed a distinct location at the tumour/stroma interface, suggesting a role for paracrine factors in the induction or maintenance of ΔNp63/p40. Thus, ΔNp63/p40 is commonly present in a small population of tumour cells with a distinct phenotype and location in ER + and/or HER2 + human breast cancers.