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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

NHERF1 and tumor microenvironment: a new scene in invasive breast carcinoma

Authors: Concetta Saponaro, Alessandro Vagheggini, Emanuela Scarpi, Matteo Centonze, Ivana Catacchio, Ondina Popescu, Maria Irene Pastena, Francesco Giotta, Nicola Silvestris, Anita Mangia

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

Tumor microenvironment (TME) includes many factors such as tumor associated inflammatory cells, vessels, and lymphocytes, as well as different signaling molecules and extracellular matrix components. These aspects can be de-regulated and consequently lead to a worsening of cancer progression. In recent years an association between the scaffolding protein Na+/H+ exchanger regulatory factor 1 (NHERF1) and tumor microenvironment changes in breast cancer (BC) has been reported.

Methods

Subcellular NHERF1 localization, vascular endothelial growth factor (VEGF), its receptor VEGFR1, hypoxia inducible factor 1 alpha (HIF-1α), TWIST1 expression and microvessel density (MVD) in 183 invasive BCs were evaluated, using immunohistochemistry on tissue microarrays (TMA). Immunofluorescence was employed to explore protein interactions.

Results

Cytoplasmic NHERF1(cNHERF1) expression was directly related to cytoplasmic VEGF and VEGFR1 expression (p = 0.001 and p = 0.027 respectively), and inversely to nuclear HIF-1α (p = 0.021) and TWIST1 (p = 0.001). Further, immunofluorescence revealed an involvement of tumor cells with NHERF1 positive staining in neo-vascular formation, suggesting a “mosaic” structure development of these neo-vessels. Survival analyses showed that loss of nuclear TWIST1 (nTWIST1) expression was related to a decrease of disease free survival (DFS) (p < 0.001), while nTWIST1-/mNHERF1+ presented an increased DFS with respect to nTWIST1+/mNHERF1- phenotype (p < 0.001). Subsequently, the analyses of nTWIST1+/cNHERF1+ phenotype selected a subgroup of patients with a worse DFS compared to nTWIST1-/cNHERF1- patients (p = 0.004).

Conclusion

Resulting data suggested a dynamic relation between NHERF1 and TME markers, and confirmed both the oncosuppressor role of membranous NHERF1 expression and the oncogene activity of cytoplasmic NHERF1.
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Metadata
Title
NHERF1 and tumor microenvironment: a new scene in invasive breast carcinoma
Authors
Concetta Saponaro
Alessandro Vagheggini
Emanuela Scarpi
Matteo Centonze
Ivana Catacchio
Ondina Popescu
Maria Irene Pastena
Francesco Giotta
Nicola Silvestris
Anita Mangia
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0766-7

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