Cargando…

Tspan8 is expressed in breast cancer and regulates E‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles

Tspan8 exhibits a functional role in many cancer types including pancreatic, colorectal, oesophagus carcinoma, and melanoma. We present a first study on the expression and function of Tspan8 in breast cancer. Tspan8 protein was present in the majority of human primary breast cancer lesions and metas...

Descripción completa

Detalles Bibliográficos
Autores principales: Voglstaetter, Maren, Thomsen, Andreas R, Nouvel, Jerome, Koch, Arend, Jank, Paul, Navarro, Elena Grueso, Gainey‐Schleicher, Tanja, Khanduri, Richa, Groß, Andrea, Rossner, Florian, Blaue, Carina, Franz, Clemens M, Veil, Marina, Puetz, Gerhard, Hippe, Andreas, Dindorf, Jochen, Kashef, Jubin, Thiele, Wilko, Homey, Bernhard, Greco, Celine, Boucheix, Claude, Baur, Andreas, Erbes, Thalia, Waller, Cornelius F, Follo, Marie, Hossein, Ghamartaj, Sers, Christine, Sleeman, Jonathan, Nazarenko, Irina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771825/
https://www.ncbi.nlm.nih.gov/pubmed/30982971
http://dx.doi.org/10.1002/path.5281
_version_ 1783455776222740480
author Voglstaetter, Maren
Thomsen, Andreas R
Nouvel, Jerome
Koch, Arend
Jank, Paul
Navarro, Elena Grueso
Gainey‐Schleicher, Tanja
Khanduri, Richa
Groß, Andrea
Rossner, Florian
Blaue, Carina
Franz, Clemens M
Veil, Marina
Puetz, Gerhard
Hippe, Andreas
Dindorf, Jochen
Kashef, Jubin
Thiele, Wilko
Homey, Bernhard
Greco, Celine
Boucheix, Claude
Baur, Andreas
Erbes, Thalia
Waller, Cornelius F
Follo, Marie
Hossein, Ghamartaj
Sers, Christine
Sleeman, Jonathan
Nazarenko, Irina
author_facet Voglstaetter, Maren
Thomsen, Andreas R
Nouvel, Jerome
Koch, Arend
Jank, Paul
Navarro, Elena Grueso
Gainey‐Schleicher, Tanja
Khanduri, Richa
Groß, Andrea
Rossner, Florian
Blaue, Carina
Franz, Clemens M
Veil, Marina
Puetz, Gerhard
Hippe, Andreas
Dindorf, Jochen
Kashef, Jubin
Thiele, Wilko
Homey, Bernhard
Greco, Celine
Boucheix, Claude
Baur, Andreas
Erbes, Thalia
Waller, Cornelius F
Follo, Marie
Hossein, Ghamartaj
Sers, Christine
Sleeman, Jonathan
Nazarenko, Irina
author_sort Voglstaetter, Maren
collection PubMed
description Tspan8 exhibits a functional role in many cancer types including pancreatic, colorectal, oesophagus carcinoma, and melanoma. We present a first study on the expression and function of Tspan8 in breast cancer. Tspan8 protein was present in the majority of human primary breast cancer lesions and metastases in the brain, bone, lung, and liver. In a syngeneic rat breast cancer model, Tspan8(+) tumours formed multiple liver and spleen metastases, while Tspan8(−) tumours exhibited a significantly diminished ability to metastasise, indicating a role of Tspan8 in metastases. Addressing the underlying molecular mechanisms, we discovered that Tspan8 can mediate up‐regulation of E‐cadherin and down‐regulation of Twist, p120‐catenin, and β‐catenin target genes accompanied by the change of cell phenotype, resembling the mesenchymal–epithelial transition. Furthermore, Tspan8(+) cells exhibited enhanced cell–cell adhesion, diminished motility, and decreased sensitivity to irradiation. As a regulator of the content and function of extracellular vesicles (EVs), Tspan8 mediated a several‐fold increase in EV number in cell culture and the circulation of tumour‐bearing animals. We observed increased protein levels of E‐cadherin and p120‐catenin in these EVs; furthermore, Tspan8 and p120‐catenin were co‐immunoprecipitated, indicating that they may interact with each other. Altogether, our findings show the presence of Tspan8 in breast cancer primary lesion and metastases and indicate its role as a regulator of cell behaviour and EV release in breast cancer. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
format Online
Article
Text
id pubmed-6771825
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley & Sons, Ltd
record_format MEDLINE/PubMed
spelling pubmed-67718252019-10-07 Tspan8 is expressed in breast cancer and regulates E‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles Voglstaetter, Maren Thomsen, Andreas R Nouvel, Jerome Koch, Arend Jank, Paul Navarro, Elena Grueso Gainey‐Schleicher, Tanja Khanduri, Richa Groß, Andrea Rossner, Florian Blaue, Carina Franz, Clemens M Veil, Marina Puetz, Gerhard Hippe, Andreas Dindorf, Jochen Kashef, Jubin Thiele, Wilko Homey, Bernhard Greco, Celine Boucheix, Claude Baur, Andreas Erbes, Thalia Waller, Cornelius F Follo, Marie Hossein, Ghamartaj Sers, Christine Sleeman, Jonathan Nazarenko, Irina J Pathol Original Papers Tspan8 exhibits a functional role in many cancer types including pancreatic, colorectal, oesophagus carcinoma, and melanoma. We present a first study on the expression and function of Tspan8 in breast cancer. Tspan8 protein was present in the majority of human primary breast cancer lesions and metastases in the brain, bone, lung, and liver. In a syngeneic rat breast cancer model, Tspan8(+) tumours formed multiple liver and spleen metastases, while Tspan8(−) tumours exhibited a significantly diminished ability to metastasise, indicating a role of Tspan8 in metastases. Addressing the underlying molecular mechanisms, we discovered that Tspan8 can mediate up‐regulation of E‐cadherin and down‐regulation of Twist, p120‐catenin, and β‐catenin target genes accompanied by the change of cell phenotype, resembling the mesenchymal–epithelial transition. Furthermore, Tspan8(+) cells exhibited enhanced cell–cell adhesion, diminished motility, and decreased sensitivity to irradiation. As a regulator of the content and function of extracellular vesicles (EVs), Tspan8 mediated a several‐fold increase in EV number in cell culture and the circulation of tumour‐bearing animals. We observed increased protein levels of E‐cadherin and p120‐catenin in these EVs; furthermore, Tspan8 and p120‐catenin were co‐immunoprecipitated, indicating that they may interact with each other. Altogether, our findings show the presence of Tspan8 in breast cancer primary lesion and metastases and indicate its role as a regulator of cell behaviour and EV release in breast cancer. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. John Wiley & Sons, Ltd 2019-06-18 2019-08 /pmc/articles/PMC6771825/ /pubmed/30982971 http://dx.doi.org/10.1002/path.5281 Text en © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Papers
Voglstaetter, Maren
Thomsen, Andreas R
Nouvel, Jerome
Koch, Arend
Jank, Paul
Navarro, Elena Grueso
Gainey‐Schleicher, Tanja
Khanduri, Richa
Groß, Andrea
Rossner, Florian
Blaue, Carina
Franz, Clemens M
Veil, Marina
Puetz, Gerhard
Hippe, Andreas
Dindorf, Jochen
Kashef, Jubin
Thiele, Wilko
Homey, Bernhard
Greco, Celine
Boucheix, Claude
Baur, Andreas
Erbes, Thalia
Waller, Cornelius F
Follo, Marie
Hossein, Ghamartaj
Sers, Christine
Sleeman, Jonathan
Nazarenko, Irina
Tspan8 is expressed in breast cancer and regulates E‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles
title Tspan8 is expressed in breast cancer and regulates E‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles
title_full Tspan8 is expressed in breast cancer and regulates E‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles
title_fullStr Tspan8 is expressed in breast cancer and regulates E‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles
title_full_unstemmed Tspan8 is expressed in breast cancer and regulates E‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles
title_short Tspan8 is expressed in breast cancer and regulates E‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles
title_sort tspan8 is expressed in breast cancer and regulates e‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771825/
https://www.ncbi.nlm.nih.gov/pubmed/30982971
http://dx.doi.org/10.1002/path.5281
work_keys_str_mv AT voglstaettermaren tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT thomsenandreasr tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT nouveljerome tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT kocharend tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT jankpaul tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT navarroelenagrueso tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT gaineyschleichertanja tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT khanduriricha tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT großandrea tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT rossnerflorian tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT blauecarina tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT franzclemensm tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT veilmarina tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT puetzgerhard tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT hippeandreas tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT dindorfjochen tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT kashefjubin tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT thielewilko tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT homeybernhard tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT grecoceline tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT boucheixclaude tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT baurandreas tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT erbesthalia tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT wallercorneliusf tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT follomarie tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT hosseinghamartaj tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT serschristine tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT sleemanjonathan tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles
AT nazarenkoirina tspan8isexpressedinbreastcancerandregulatesecadherincateninsignallingandmetastasisaccompaniedbyincreasedcirculatingextracellularvesicles