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...

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Bibliographic Details
Published in:	Journal of cellular and molecular medicine Vol. 11; no. 4; pp. 826 - 838
Main Authors:	Jones, Jon, Berkhoff, Stefan, Weich, Eva, Engl, Tobias, Wedel, Steffen, Relja, Borna, Jonas, Dietger, A.Blaheta, Roman
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-07-2007 John Wiley & Sons, Inc
Subjects:	14-3-3 protein adhesion beta1 integrins Biotechnology Breast cancer Cancer Cell Adhesion Cell adhesion & migration Cell adhesion molecules Cell culture Cell cycle Cell Cycle Proteins - metabolism Cell growth Cell Line, Tumor Cell Membrane - metabolism Cell membranes Cell migration Cloning Down-Regulation Endothelial cells Endothelial Cells - enzymology Endothelial Cells - metabolism Endothelium Extracellular matrix Flow Cytometry Focal adhesion kinase Focal Adhesion Protein-Tyrosine Kinases - metabolism Gene Expression Regulation, Neoplastic Humans HUVEC Integrin beta1 - genetics Integrin beta1 - metabolism Integrins Intracellular signalling Kidney diseases Kidney Neoplasms - genetics Kidney Neoplasms - metabolism Kinases membrane fragments Membranes Metastases Metastasis Microscopy, Confocal Monoclonal antibodies Prostate Protein kinase C Proteins Renal cell carcinoma Signal Transduction signalling proteins Subcellular Fractions - metabolism Sucrose Tumor cell lines Tumors Umbilical Cord - cytology Umbilical Cord - enzymology Berlin Germany Germany
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1582-1838 1582-4934
DOI:	10.1111/j.1582-4934.2007.00071.x