S100P and Ezrin promote trans-endothelial migration of triple negative breast cancer cells
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 f...
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Published in | Cellular oncology (Dordrecht) Vol. 42; no. 1; pp. 67 - 80 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Dordrecht
Springer Netherlands
01.02.2019
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | 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 Ezrin
Thr-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 Ezrin
Thr-567
immunoreactivity significantly correlated with vascular invasion in TNBC patients.
Conclusions
From our data we conclude that S100P, Ezrin and Ezrin
Thr-567
are involved in the trans-endothelial migration of TNBC cells and that they may serve as potential targets in TNBC patients. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2211-3428 2211-3436 |
DOI: | 10.1007/s13402-018-0408-2 |