Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Cellular Oncology
Erschienen in: Cellular Oncology 1/2019

22.09.2018 | Original Paper

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

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

Erschienen in: Cellular Oncology | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
K.R. Bauer, M. Brown, R.D. Cress, C.A. Parise, V. Caggiano, Descriptive analysis of estrogen receptor (ER)- negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype. Cancer 109, 1721–1728 (2007)CrossRefPubMed
2.
M.D. Laurentiis, D. Cianniello, R. Caputo, B. Stanzione, G. Arpino, S. Cinieri, V. Lorusso, S.D. Placido, Treatment of triple negative breast cancer (TNBC): Current options and future perspectives. Cancer Treat Rev 36, S80–S86 (2010)CrossRefPubMed
3.
R. Rouzier, C.M. Perou, W.F. Symmans, N. Ibrahim, M. Cristofanilli, K. Anderson, K.R. Hess, J. Stec, M. Ayers, P. Wagner, P. Morandi, C. Fan, I. Rabiul, J.S. Ross, G.N. Hortobagyi, L. Pusztai, Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11, 5678–5685 (2005)CrossRefPubMed
4.
C. Liedtke, C. Mazouni, K.R. Hess, F. Andre, A. Tordai, J.A. Mejia, W.F. Symmans, A.M. Gonzalez-Angulo, B. Hennessy, M. Green, M. Cristofanilli, G.N. Hortobagyi, L. Pusztai, Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26, 1275–1281 (2008)CrossRefPubMed
5.
R. Dent, M. Trudeau, K.I. Pritchard, W.M. Hanna, H.K. Kahn, C.A. Sawka, L.A. Lickley, E. Rawlinson, P. Sun, S.A. Narod, Triple-negative breast cancer; clinical features and patterns of recurrence. Clin Cancer Res 13, 4429–4435 (2007)CrossRefPubMed
6.
M. Yousefi, R. Nosrati, A. Salmaninejad, S. Dehghani, A. Shahryari, A. Saberi, Organ-specific metastasis of breast cancer: Molecular and cellular mechanisms underlying lung metastasis. Cell Oncol 41, 123–140 (2018)CrossRef
7.
R. Sharma, R. Sharma, T.P. Khaket, C. Dutta, B. Chakraborty, T.K. Mukherjee, Breast cancer metastasis: Putative therapeutic role of vascular cell adhesion molecule-1. Cell Oncol 40, 199–208 (2017)CrossRef
8.
T. Arumugam, C.D. Logsdon, S100P: A novel therapeutic target for cancer. Amino Acids 41, 893–899 (2011)CrossRefPubMed
9.
F. Prica, T. Radon, Y. Cheng, T. Crnogorac-Jurcevic, The life and works of S100P - from conception to cancer. Am J Cancer Res 6, 562–576 (2016)PubMedPubMedCentral
10.
A. Maciejczyk, A. Łacko, M. Ekiert, E. Jagoda, T. Wysocka, R. Matkowski, A. Hałoń, B. Györffy, H. Lage, P. Surowiak, Elevated nuclear S100P expression is associated with poor survival in early breast cancer patients. Histol Histopathol 28, 513–524 (2013)PubMed
11.
L. Chung, L. Phillips, M.Z. Lin, K. Moore, D.J. Marsh, F.M. Boyle, R.C. Baxter, A novel truncated form of S100P predicts disease-free survival in patients with lymph node positive breast cancer. Cancer Lett 368, 64–70 (2015)CrossRefPubMed
12.
S. Zhang, Z. Wang, W. Liu, R. Lei, J. Shan, L. Li, X. Wang, Distinct prognostic values of S100 mRNA expression in breast cancer. Sci Rep 7, 39786 (2017)CrossRefPubMedPubMedCentral
13.
T. Becker, V. Gerke, E. Kube, K. Weber, S100P, a novel Ca2+-binding protein from human placenta. cDNA cloning, recombinant protein expression and Ca2+ binding properties. Eur J Biochem 207, 541–547 (1992)CrossRefPubMed
14.
S. Parkkila, P. Pan, A. Ward, A. Gibadulinova, I. Oveckova, S. Pastorekova, J. Pastorek, A.R. Martinez, H.O. Helin, J. Isola, The calcium-binding protein S100P in normal and malignant human tissues. BMC Clin Pathol 8, 2 (2008)CrossRefPubMedPubMedCentral
15.
M. Komatsu, T. Yoshimura, T. Matsuo, K. Kiyotani, Y. Miyoshi, T. Tanihashi, K. Rokutani, R. Yamaguchi, A. Saito, S. Imoto, S. Miyano, Y. Nakamura, M. Sasa, M. Shimada, T. Katagiri, Molecular features of triple negative breast cancer cells by genome-wide gene expression profiling analysis. Int J Oncol 42, 478–506 (2013)CrossRefPubMed
16.
M. Maierthaler, M. Kriegsmann, C. Peng, S. Jauch, A. Szabo, M. Wallwiener, J. Rom, C. Sohn, A. Schneeweiss, H. Sinn, R. Yang, B. Burwinkel, S100P and HYAL2 as prognostic markers for patients with triple-negative breast cancer. Exp Mol Pathol 99, 180–187 (2015)CrossRefPubMed
17.
Q. Li, M. Wu, H. Wang, G. Xu, T. Zhu, Y. Zhang, P. Liu, A. Song, C. Gang, Z. Han, J. Zhou, L. Meng, Y. Lu, S. Wang, D. Ma, Ezrin silencing by small hairpin RNA reverses metastatic behaviors of human breast cancer cells. Cancer Lett 261, 55–63 (2008)CrossRefPubMed
18.
S.D. Choi, Ezrin is an essential marker for metastasis of gynecologic cancer. J Korean Soc Menopause 18, 81–93 (2012)CrossRef
19.
J. Clucas, F. Valderrama, ERM proteins in cancer progression. J Cell Sci 127, 267–275 (2014)CrossRefPubMed
20.
T. Matsui, M. Maeda, Y. Doi, S. Yonemura, M. Amano, K. Kaibuchi, S. Tsukita, S. Tsukita, Rho-kinase phosphorylates COOH-terminal threonines of Ezrin/Radixin/Moesin (ERM) proteins and regulates their head-to-tail association. J Cell Biol 140, 647–657 (1998)CrossRefPubMedPubMedCentral
21.
A. Gautreau, D. Louvard, M. Arpin, Morphogenic effects of Ezrin require a phosphorylation-induced transition from oligomers to monomers at the plasma membrane. J Cell Biol 150, 193–203 (2000)CrossRefPubMedPubMedCentral
22.
J. Li, K. Wei, H. Yu, D. Jin, G. Wang, B. Yu, Prognostic value of Ezrin in various cancers: A systematic review and updated meta-analysis. Sci Rep 5, 17903 (2015)CrossRefPubMedPubMedCentral
23.
M. Bartova, J. Hlavaty, Y. Tan, C. Singer, K. Pohlodek, J. Luha, I. Walter, Expression of Ezrin and Moesin in primary breast carcinoma and matched lymph node metastases. Clin Exp Metastasis. 34, 333–344 (2017)CrossRefPubMed
24.
T. Jin, J. Jin, X. Li, S. Zhang, Y.H. Choi, Y. Piao, X. Shen, Z. Lin, Prognostic implications of Ezrin and phosphorylated Ezrin expression in non-small cell lung cancer. BMC Cancer 14, 191 (2014)CrossRefPubMedPubMedCentral
25.
J. He, G. Ma, J. Qian, Y. Zhu, M. Liang, N. Yao, Q. Ding, L. Chen, X. Liu, T. Xia, S. Wang, Interaction between Ezrin and Cortactin in promoting epithelial to mesenchymal transition in breast cancer cells. Med Sci Monit 23, 1583–1596 (2017)CrossRefPubMedPubMedCentral
26.
M. Koltzscher, C. Neumann, S. Konig, V. Gerke, Ca2+-dependent binding and activation of dormant Ezrin by dimeric S100P. Mol Biol Cell 14, 2372–2384 (2003)CrossRefPubMedPubMedCentral
27.
H. Zhang, G. Wang, Y. Ding, Z. Wang, R. Barraclough, P.S. Rudland, D.G. Fernig, Z. Rao, The crystal structure at 2A resolution of the Ca2+-binding protein S100P. J Mol Biol 325, 785–794 (2003)CrossRefPubMed
28.
A. Gibadulinova, V. Tothova, J. Pastorek, S. Pastorekova, Transcriptional regulation and functional implication of S100P in cancer. Amino Acids 41, 885–892 (2011)CrossRefPubMed
29.
S. Diederichs, E. Bulk, B. Steffen, P. Ji, L. Tickenbrock, K. Lang, K.S. Zanker, R. Metzger, P.M. Schneider, V. Gerke, M. Thomas, W.E. Berdel, H. Serve, C. Muller-Tidow, S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer. Cancer Res 64, 5564–5569 (2004)CrossRefPubMed
30.
J. Austermann, A.R. Nazmi, C. Muller-Tidow, V. Gerke, Characterization of the Ca2+-regulated Ezrin-S100P interaction and its role in tumor cell migration. J Biochem 283, 29331–29340 (2008)
31.
S. Barry, C. Chelala, K. Lines, M. Sunamura, A. Wang, F.M. Marelli-Berg, C. Brennan, N.R. Lemoine, T. Crnogorac-Jurcevic, S100P is a metastasis-associated gene that facilitates transendothelial migration of pancreatic cancer cells. Clin Exp Metastasis 30, 251–264 (2013)CrossRefPubMed
32.
C. Artus, F. Glacial, K. Ganeshamoorthy, N. Ziegler, M. Godet, T. Guilbert, S. Liebner, P. Couraud, The Wnt/planar cell polarity signaling pathway contributes to the integrity of tight junctions in brain endothelial cells. J Cerebr Blood F Met 34, 433–440 (2014)CrossRef
33.
N. Maishi, Y. Ohba, K. Akiyama, N. Ohga, J. Hamada, H. Nagao-Kitamoto, M.T. Alam, K. Yamamoto, T. Kawamoto, N. Inoue, A. Taketomi, M. Shindoh, Y. Hida, K. Hida, Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan. Sci Reports 6, 28039 (2016)CrossRef
34.
J.M. Iglesias, I. Beloqui, F. Garcia-Garcia, O. Leis, A. Vazquez- Martin, A. Eguiara, S. Cufi, A. Pavon, J.A. Menendez, J. Dopazo, A.G. Martin, Mammosphere formation in breast carcinoma cell lines depends upon expression of E-cadherin. PLoS One e77281, 8 (2013)
35.
D. Sarrio, S.M. Marıa, A. Dotor, F. Calero, D. Hardisson, J. Palacios, Abnormal ezrin localization is associated with clinicopathological features in invasive breast carcinomas. Breast cancer Res Tr 98, 71–79 (2006)CrossRef
36.
A.P.T. Schor, F.M. Carvalho, C. Kemp, I.D.C.G. Silva, J. Russo, S100P calcium-binding protein expression is associated with high-risk proliferative lesions of the breast. Oncol Rep 15, 3–6 (2006)PubMed
37.
L. Guo, S. Chen, H. Jiang, J. Huang, W. Jin, S. Yao, The expression of S100P increases and promotes cellular proliferation by increasing nuclear translocation of β-catenin in endometrial cancer. Int J Clin Exp Pathol 7, 2102–2112 (2014)PubMedPubMedCentral
38.
Y. Liu, C. Wang, X. Shan, J. Wu, H. Liu, H. Liu, J. Zhang, W. Xu, Z. Sha, J. He, J. Fan, S100P is associated with proliferation and migration in nasopharyngeal carcinoma. Oncology Lett 14, 525–532 (2017)CrossRef
39.
S. Dakhel, L. Padilla, J. Adan, M. Masa, J.M. Martinez, L. Roque, T. Coll, R. Hervas, C. Calvis, R. Messeguer, F. Mitjans, J.L. Hernandez, S100P antibody-mediated therapy as a new promising strategy for the treatment of pancreatic cancer. Oncogene 3, e92 (2014)CrossRef
40.
J.K. Kim, K.H. Jung, J.H. Noh, J.W. Eun, H.J. Bae, H.J. Xie, Y.M. Ahn, J.C. Ryu, W.S. Park, J.Y. Lee, S.W. Nam, Targeted disruption of S100P suppresses tumor cell growth by down-regulation of cyclin D1 and CDK2 in human hepatocellular carcinoma. Int J Oncol 35, 1257–1264 (2009)PubMed
41.
X. Wang, T. Tian, M. Zhao, Y. Lou, J. Qian, Z. Liu, H. Chen, Z. Cui, High expression of S100P is associated with unfavorable prognosis and tumor progression in patients with epithelial ovarian cancer. Am J Cancer Res 5, 2409–2421 (2015)PubMedPubMedCentral
42.
G.D. Basu, D.O. Azorsa, J.A. Kiefer, A.M. Rojas, S. Tuzmen, M.T. Barrett, J.M. Trent, O. Kallioniemi, S. Mousses, Functional evidence implicating S100P in prostate cancer progression. Int J Cancer 123, 330–339 (2008)CrossRefPubMed
43.
A. Chandramouli, M.E. Mercado-Pimentel, A. Hutchinson, A. Gibadulinová, E.R. Olson, S. Dickinson, R. Shañas, J. Davenport, J. Owens, A.K. Bhattacharyya, J.W. Regan, S. Pastorekova, T. Arumugam, C.D. Logsdon, M.A. Nelson, The induction of S100p expression by the Prostaglandin E2 (PGE2 )/EP4 receptor signaling pathway in colon cancer cells. Cancer Biol Ther 10, 1056–1066 (2010)CrossRefPubMedPubMedCentral
44.
M.E. Mercado-Pimentel, B.C. Onyeagucha, Q. Li, A.C. Pimentel, J. Jandova, M.A. Nelson, The S100P/RAGE signaling pathway regulates expression of microRNA-21 in colon cancer cells. FEBS Lett 589, 2388–2393 (2015)CrossRefPubMedPubMedCentral
45.
Z. Wu, T. Boonmars, I. Nagano, S. Boonjaraspinyo, P. Srinontong, P. Ratasuwan, K. Narong, P.S. Nielsen, Y. Maekawa, Significance of S100P as a biomarker in diagnosis, prognosis and therapy of opisthorchiasis-associated cholangiocarcinoma. Int J Cancer 138, 396–408 (2015)CrossRefPubMed
46.
C. Zhou, Q. Zhong, L.V. Rhodes, I. Townley, M.R. Bratton, Q. Zhang, E.C. Martin, S. Elliott, B.M. Collins-Burow, M.E. Burow, G. Wang, Proteomic analysis of acquired tamoxifen resistance in MCF-7 cells reveals expression signatures associated with enhanced migration. Breast Cancer Res 14, R45 (2012)CrossRefPubMedPubMedCentral
47.
T. Arumugam, D.M. Simeone, A.M. Schmidt, C.D. Logsdon, S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE). J Biol Chem 279, 5059–5065 (2004)CrossRefPubMed
48.
Y. Chen, D. Wang, Z. Guo, J. Zhao, B. Wu, H. Deng, T. Zhou, H. Xiang, F. Gao, X. Yu, J. Liao, T. Ward, P. Xia, C. Emenari, X. Ding, W. Thompson, K. Ma, J. Zhu, F. Aikhionbare, K. Dou, S.Y. Cheng, X. Yao, Rho kinase phosphorylation promotes Ezrin-mediated metastasis in hepatocellular carcinoma. Cancer Res 71, 1721–1730 (2011)CrossRefPubMedPubMedCentral
49.
S. Giampieri, C. Manning, S. Hooper, L. Jones, C.S. Hill, E. Sahai, Localized and reversible TGFβ signalling switches breast cancer cells from cohesive to single cell motility. Nat Cell Biol 11, 1287–1296 (2009)CrossRefPubMedPubMedCentral
50.
Y.L. Hsu, J.Y. Hung, Y.Y. Liang, Y.S. Lin, M.J. Tsai, S.H. Chou, C.Y. Lu, P.L. Kuo, S100P interacts with integrin α7 and increases cancer cell migration and invasion in lung cancer. Oncotarget 6, 29585–29598 (2015)PubMedPubMedCentral
51.
L.L. Cao, J.W. Xie, Y. Lin, C.H. Zheng, P. Li, J.B. Wang, J.X. Lin, J. Lu, Q.Y. Chen, C.M. Huang, miR-183 inhibits invasion of gastric cancer by targeting Ezrin. Int J Clin Exp Pathol 7, 5582–5594 (2014)PubMedPubMedCentral
52.
Y. Li, Z. Lin, B. Chen, S. Chen, Z. Jiang, T. Zhou, Z. Hou, Y. Wang, Ezrin/NF-kB activation regulates epithelial- mesenchymal transition induced by EGF and promotes metastasis of colorectal cancer. Biomed Pharmacother 92, 140–148 (2017)CrossRefPubMed
53.
S. Hamada, K. Satoh, M. Hirota, W. Fujibuchi, A. Kanno, J. Umino, H. Ito, A. Satoh, K. Kikuta, K. Kume, A. Masamune, T. Shimosegawa, Expression of the calcium-binding protein S100P is regulated by bone morphogenetic protein in pancreatic duct epithelial cell lines. Cancer Sci 100, 103–110 (2008)CrossRefPubMed
Metadaten
Titel
S100P and Ezrin promote trans-endothelial migration of triple negative breast cancer cells
verfasst von
Kyoko Kikuchi
Keely May McNamara
Yasuhiro Miki
Erina Iwabuchi
Ayako Kanai
Minoru Miyashita
Takanori Ishida
Hironobu Sasano
Publikationsdatum
22.09.2018
Verlag
Springer Netherlands
Erschienen in
Cellular Oncology / Ausgabe 1/2019
Print ISSN: 2211-3428
Elektronische ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-018-0408-2

Weitere Artikel der Ausgabe 1/2019

Cellular Oncology 1/2019 Zur Ausgabe

Original Paper

CCR5 blockage by maraviroc: a potential therapeutic option for metastatic breast cancer

Original Paper

Radio-sensitization of head and neck cancer cells by a combination of poly(I:C) and cisplatin through downregulation of survivin and c-IAP2

Review

Cell-free DNA in cancer: current insights

Review

Long non-coding RNAs as monitoring tools and therapeutic targets in breast cancer

Original Paper

CCL18 secreted from M2 macrophages promotes migration and invasion via the PI3K/Akt pathway in gallbladder cancer

Report

Molecular features unique to glioblastoma radiation resistant residual cells may affect patient outcome - a short report

Neu im Fachgebiet Pathologie

01.04.2024 | Forensische Traumatologie | CME

Theoretische Grundlagen von Explosionen und Explosionsverletzungen

Open Access 22.02.2024 | Pathologie | Originalien

Auswirkungen vorgeschalteter Laborprozesse auf die Digitalisierung histologischer Schnittpräparate

21.02.2024 | Thrombozytopenie | CME

Knochenmarkhistologie bei Zytopenien
Beitrag zur hämatologischen Differenzialdiagnostik

Open Access 21.02.2024 | Fettleber | Originalien

Herausforderungen der Automation bei der quantitativen Auswertung von Leberbiopsien
Automatische Quantifizierung von Leberverfettung