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Cellular Oncology
Published in: Cellular Oncology 1/2019

01-02-2019 | Original Paper

S100P and Ezrin promote trans-endothelial migration of triple negative breast cancer cells

Authors: Kyoko Kikuchi, Keely May McNamara, Yasuhiro Miki, Erina Iwabuchi, Ayako Kanai, Minoru Miyashita, Takanori Ishida, Hironobu Sasano

Published in: Cellular Oncology | Issue 1/2019

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Abstract

Purpose

Triple negative breast cancer (TNBC) patients generally have an adverse clinical outcome because their tumors often recur and metastasize to distant sites in the first 3 years after surgery. Therefore, it has become pivotal to identify potential factors associated with metastasis. Here, we focused on the effects of S100P and Ezrin on the trans-endothelial migration (TEM) of TNBC cells, as they have both been suggested to play a role in this process in other malignancies.

Methods

The expression of S100P and Ezrin was examined by immunohistochemistry in 58 primary TNBC samples. The mRNA and protein levels of S100P and Ezrin were assessed in breast cancer-derived cell lines using qRT-PCR and Western blotting, respectively. Proliferation and migration assays were performed using TNBC-derived MFM-223 and SUM-185-PE cells transfected with S100P and Ezrin siRNAs. Two different timeframes were employed for TEM assays using TNBC-derived cells and human umbilical vein endothelial-derived cells, respectively. Correlations between the status of EzrinThr-567 expression and various clinicopathological features were analyzed by immunohistochemistry.

Results

We found that S100P and Ezrin double negative TNBC cases were significantly associated with a better disease-free survival. We also found that single and double siRNA-mediated knockdown of S100P and Ezrin in TNBC-derived cells significantly inhibited their TEM and destabilized the intercellular junctions of endothelial cells. In addition, we found that EzrinThr-567 immunoreactivity significantly correlated with vascular invasion in TNBC patients.

Conclusions

From our data we conclude that S100P, Ezrin and EzrinThr-567 are involved in the trans-endothelial migration of TNBC cells and that they may serve as potential targets in TNBC patients.
Appendix
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Metadata
Title
S100P and Ezrin promote trans-endothelial migration of triple negative breast cancer cells
Authors
Kyoko Kikuchi
Keely May McNamara
Yasuhiro Miki
Erina Iwabuchi
Ayako Kanai
Minoru Miyashita
Takanori Ishida
Hironobu Sasano
Publication date
01-02-2019
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 1/2019
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-018-0408-2

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