Cargando…

Transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes

Adhesion molecules of the integrin beta1 family are thought to be involved in the malignant progression renal cell carcinoma (RCC). Still, it is not clear how they contribute to this process. Since the hematogenous phase of tumour dissemination is the rate-limiting step in the metastatic process, we...

Descripción completa

Detalles Bibliográficos
Autores principales: Jones, Jon, Berkhoff, Stefan, Weich, Eva, Engl, Tobias, Wedel, Steffen, Relja, Borna, Jonas, Dietger, ABlaheta, Roman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823260/
https://www.ncbi.nlm.nih.gov/pubmed/17760843
http://dx.doi.org/10.1111/j.1582-4934.2007.00071.x
_version_ 1782290539718115328
author Jones, Jon
Berkhoff, Stefan
Weich, Eva
Engl, Tobias
Wedel, Steffen
Relja, Borna
Jonas, Dietger
ABlaheta, Roman
author_facet Jones, Jon
Berkhoff, Stefan
Weich, Eva
Engl, Tobias
Wedel, Steffen
Relja, Borna
Jonas, Dietger
ABlaheta, Roman
author_sort Jones, Jon
collection PubMed
description Adhesion molecules of the integrin beta1 family are thought to be involved in the malignant progression renal cell carcinoma (RCC). Still, it is not clear how they contribute to this process. Since the hematogenous phase of tumour dissemination is the rate-limiting step in the metastatic process, we explored beta1 integrin alterations on several RCC cell lines (A498, Caki1, KTC26) before and after contacting vascular endothelium in a tumour-endothelium (HUVEC) co-culture assay. Notably, alpha2, alpha3 and alpha5 integrins became down-regulated immediately after the tumour cells attached to HUVEC, followed by re-expression shortly thereafter. Integrin down-regulation on RCC cells was caused by direct contact with endothelial cells, since the isolated endothelial membrane fragments but not the cell culture supernatant contributed to the observed effects. Integrin loss was accompanied by a reduced focal adhesion kinase (FAK) expression, FAK activity and diminished binding of tumour cells to matrix proteins. Furthermore, intracellular signalling proteins RCC cells were altered in the presence of HUVEC membrane fragments, in particular 14-3-3 epsilon, ERK2, PKCdelta, PKCepsilon and RACK1, which are involved in regulating tumour cell motility. We, therefore, speculate that contact of RCC cells with the vascular endothelium converts integrin-dependent adhesion to integrin-independent cell movement. The process of dynamic integrin regulation may be an important part in tumour cell migration strategy, switching the cells from being adhesive to becoming motile and invasive.
format Online
Article
Text
id pubmed-3823260
institution National Center for Biotechnology Information
language English
publishDate 2007
publisher Blackwell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-38232602015-04-27 Transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes Jones, Jon Berkhoff, Stefan Weich, Eva Engl, Tobias Wedel, Steffen Relja, Borna Jonas, Dietger ABlaheta, Roman J Cell Mol Med Articles Adhesion molecules of the integrin beta1 family are thought to be involved in the malignant progression renal cell carcinoma (RCC). Still, it is not clear how they contribute to this process. Since the hematogenous phase of tumour dissemination is the rate-limiting step in the metastatic process, we explored beta1 integrin alterations on several RCC cell lines (A498, Caki1, KTC26) before and after contacting vascular endothelium in a tumour-endothelium (HUVEC) co-culture assay. Notably, alpha2, alpha3 and alpha5 integrins became down-regulated immediately after the tumour cells attached to HUVEC, followed by re-expression shortly thereafter. Integrin down-regulation on RCC cells was caused by direct contact with endothelial cells, since the isolated endothelial membrane fragments but not the cell culture supernatant contributed to the observed effects. Integrin loss was accompanied by a reduced focal adhesion kinase (FAK) expression, FAK activity and diminished binding of tumour cells to matrix proteins. Furthermore, intracellular signalling proteins RCC cells were altered in the presence of HUVEC membrane fragments, in particular 14-3-3 epsilon, ERK2, PKCdelta, PKCepsilon and RACK1, which are involved in regulating tumour cell motility. We, therefore, speculate that contact of RCC cells with the vascular endothelium converts integrin-dependent adhesion to integrin-independent cell movement. The process of dynamic integrin regulation may be an important part in tumour cell migration strategy, switching the cells from being adhesive to becoming motile and invasive. Blackwell Publishing Ltd 2007-07 2007-06-24 /pmc/articles/PMC3823260/ /pubmed/17760843 http://dx.doi.org/10.1111/j.1582-4934.2007.00071.x Text en
spellingShingle Articles
Jones, Jon
Berkhoff, Stefan
Weich, Eva
Engl, Tobias
Wedel, Steffen
Relja, Borna
Jonas, Dietger
ABlaheta, Roman
Transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes
title Transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes
title_full Transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes
title_fullStr Transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes
title_full_unstemmed Transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes
title_short Transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes
title_sort transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823260/
https://www.ncbi.nlm.nih.gov/pubmed/17760843
http://dx.doi.org/10.1111/j.1582-4934.2007.00071.x
work_keys_str_mv AT jonesjon transientdownregulationofbeta1integrinsubtypesonkidneycarcinomacellsisinducedbymechanicalcontactwithendothelialcellmembranes
AT berkhoffstefan transientdownregulationofbeta1integrinsubtypesonkidneycarcinomacellsisinducedbymechanicalcontactwithendothelialcellmembranes
AT weicheva transientdownregulationofbeta1integrinsubtypesonkidneycarcinomacellsisinducedbymechanicalcontactwithendothelialcellmembranes
AT engltobias transientdownregulationofbeta1integrinsubtypesonkidneycarcinomacellsisinducedbymechanicalcontactwithendothelialcellmembranes
AT wedelsteffen transientdownregulationofbeta1integrinsubtypesonkidneycarcinomacellsisinducedbymechanicalcontactwithendothelialcellmembranes
AT reljaborna transientdownregulationofbeta1integrinsubtypesonkidneycarcinomacellsisinducedbymechanicalcontactwithendothelialcellmembranes
AT jonasdietger transientdownregulationofbeta1integrinsubtypesonkidneycarcinomacellsisinducedbymechanicalcontactwithendothelialcellmembranes
AT ablahetaroman transientdownregulationofbeta1integrinsubtypesonkidneycarcinomacellsisinducedbymechanicalcontactwithendothelialcellmembranes