%0 Journal Article
%T Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy
%A Tobias Engl
%A Jasmina Makarevi£¿
%A Borna Relja
%A Iyad Natsheh
%A Iris M¨¹ller
%A Wolf-Dietrich Beecken
%A Dietger Jonas
%A Roman A Blaheta
%J BMC Cancer
%D 2005
%I BioMed Central
%R 10.1186/1471-2407-5-4
%X Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 ¦ÌM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a), alpha2beta1 (CD49b), alpha3beta1 (CD49c), alpha4beta1 (CD49d), alpha5beta1 (CD49e), and alpha6beta1 (CD49f) receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry.Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 ¦ÌM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes.We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype.With the improved long-term outcome of allograft recipients in the cyclosporine or tacrolimus era, malignant tumors have become increasingly important. Malignant tumours develop in 15¨C20% of graft recipients after 10 years, and thus contribute substantially to the morbidity and mortality of these patients [1]. Malignancies can develop in three ways: de-novo occurrence in the recipient, recurrent malignancy in the recipient or transmission of malignancy from the donor. In all cases, the post-transplant treatment regimen and the level of immunosuppression are high risk factors due to the long-term modification of the immune system.During the
%U http://www.biomedcentral.com/1471-2407/5/4