TY  - JOUR
A1  - Jones, Jon
A1  - Berkhoff, Stefan
A1  - Jüngel, Eva
A1  - Engl, Tobias A.
A1  - Wedel, Steffen Alexander
A1  - Relja, Borna
A1  - Jonas, Dietger
A1  - Blaheta, Roman A.
T1  - Transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes
T2  - Journal of cellular and molecular medicine
N2  - 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.
KW  - adhesion
KW  - beta1 integrins
KW  - HUVEC
KW  - membrane fragments
KW  - renal cell carcinoma
KW  - signalling proteins
Y1  - 2007
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28375
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-283755
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823260/
SN  - 1582-4934
SN  - 1582-1838
N1  - 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.
VL  - 11
IS  - 4
SP  - 826
EP  - 838
PB  - Wiley-Blackwell
CY  - Hoboken, NJ
ER  -