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
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.
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Metadaten
Author:Jon Jones, Stefan Berkhoff, Eva Jüngel, Tobias A. Engl, Steffen Alexander Wedel, Borna Relja, Dietger Jonas, Roman A. Blaheta
URN:urn:nbn:de:hebis:30:3-283755
URL:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823260/
DOI:http://dx.doi.org/10.1111/j.1582-4934.2007.00071.x
ISSN:1582-4934
ISSN:1582-1838
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=17760843
Parent Title (English):Journal of cellular and molecular medicine
Publisher:Wiley-Blackwell
Place of publication:Hoboken, NJ
Document Type:Article
Language:English
Date of Publication (online):2007/06/24
Date of first Publication:2007/06/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2013/02/08
Tag:HUVEC; adhesion; beta1 integrins; membrane fragments; renal cell carcinoma; signalling proteins
Volume:11
Issue:4
Pagenumber:13
First Page:826
Last Page:838
Note:
This is an Open Access article under the terms of the Creative Commons Attribution Non Commercial License http://creativecommons.org/licenses/by-nc/3.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
HeBIS PPN:327997672
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0

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