Kyoko Kikuchi1, Keely May McNamara1, Yasuhiro Miki2, Erina Iwabuchi1, Ayako Kanai1,3, Minoru Miyashita3, Takanori Ishida3, Hironobu Sasano4. 1. Department of Pathology, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku Sendai-shi, Miyagi, 980-8575, Japan. 2. Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science (IRIDeS), Tohoku University, 2-1, Seiryo-machi, Aoba-ku Sendai-shi, Miyagi, 980-8575, Japan. 3. Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku Sendai-shi, Miyagi, 980-8575, Japan. 4. Department of Pathology, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku Sendai-shi, Miyagi, 980-8575, Japan. hsasano@patholo2.med.tohoku.ac.jp.
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.
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.
Entities:
Keywords:
Ezrin; S100P; Trans-endothelial migration; Triple negative breast carcinoma
Authors: Roman Rouzier; Charles M Perou; W Fraser Symmans; Nuhad Ibrahim; Massimo Cristofanilli; Keith Anderson; Kenneth R Hess; James Stec; Mark Ayers; Peter Wagner; Paolo Morandi; Chang Fan; Islam Rabiul; Jeffrey S Ross; Gabriel N Hortobagyi; Lajos Pusztai Journal: Clin Cancer Res Date: 2005-08-15 Impact factor: 12.531
Authors: Liping Chung; Leo Phillips; Mike Z Lin; Katrina Moore; Deborah J Marsh; Frances M Boyle; Robert C Baxter Journal: Cancer Lett Date: 2015-08-11 Impact factor: 8.679
Authors: Rebecca Dent; Maureen Trudeau; Kathleen I Pritchard; Wedad M Hanna; Harriet K Kahn; Carol A Sawka; Lavina A Lickley; Ellen Rawlinson; Ping Sun; Steven A Narod Journal: Clin Cancer Res Date: 2007-08-01 Impact factor: 12.531
Authors: M De Laurentiis; D Cianniello; R Caputo; B Stanzione; G Arpino; S Cinieri; V Lorusso; S De Placido Journal: Cancer Treat Rev Date: 2010-11 Impact factor: 12.111
Authors: Adam Maciejczyk; Aleksandra Łacko; Marcin Ekiert; Ewa Jagoda; Teresa Wysocka; Rafał Matkowski; Agnieszka Hałoń; Balázs Györffy; Hermann Lage; Paweł Surowiak Journal: Histol Histopathol Date: 2013-01-31 Impact factor: 2.303
Authors: Cornelia Liedtke; Chafika Mazouni; Kenneth R Hess; Fabrice André; Attila Tordai; Jaime A Mejia; W Fraser Symmans; Ana M Gonzalez-Angulo; Bryan Hennessy; Marjorie Green; Massimo Cristofanilli; Gabriel N Hortobagyi; Lajos Pusztai Journal: J Clin Oncol Date: 2008-02-04 Impact factor: 44.544