Carcinogenesis Advance Access published online on August 29, 2003
Carcinogenesis, doi:10.1093/carcin/bgg148
© 2003 by Oxford University Press
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CANCER BIOLOGY
1 Technische Universität München, Klinikum rechts der Isar, Institut für Allgemeine Pathologie und Pathologische Anatomie, München, Germany; GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Pathologie, Neuherberg, Germany
* Corresponding author. E-mail: luber{at}lrz.tum.de.
Received 20 March 2003
; revised 19 June 2003
; accepted 6 August 2003
In this study, we investigated whether tumor-associated E-cadherin mutations impair the tumor-suppressive function of the cell adhesion molecule and influence metastasis formation in a severe combined immunodeficiency mouse model. The investigated E-cadherin mutations were in frame deletions of exons 8 (del 8) or 9 (del 9) and a point mutation in exon 8 (p8). Transfected human MDA-MB-435S carcinoma cells stably expressing wild-type (wt) or mutant E-cadherin were injected into the mouse mammary fat pad. Mice transplanted with wt E-cadherin transfectants developed significantly smaller tumors than animals transplanted with the E-cadherin-negative parental cell line. Animals transplanted with del 9 or p8 E-cadherin transfectants produced medium size tumors, indicating that these mutations impair the tumor - suppressive function of E-cadherin. In contrast, mice transplanted with del 8 E-cadherin transfectants developed tumors of approximately the same sizes as animals transplanted with wt E-cadherin expressing cells. Lung metastases were induced by all cell lines without significant differences. Immunohistochemical analysis of E-cadherin expression in the tumors revealed a heterogeneous staining pattern, indicating loss or down-regulation of E-cadherin in some tumor cells. Metastases were completely negative for E-cadherin. Our data suggest that the type of mutation determines whether the tumor-suppressive function of E-cadherin is impaired.
E-cadherin mutations, tumor, metastasis, SCID mouse, xenotransplantation
Influence of tumor-associated E-cadherin mutations on tumorigenicity and metastasis
2 GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Pathologie, Neuherberg, Germany
3 Technische Universität München, Klinikum rechts der Isar, Institut für Allgemeine Pathologie und Pathologische Anatomie, München, Germany
4 Department of Pathology, Instituto Nacional de la Nutricion Salvador Zubiran, Mexico, D.F., Mexico
5 Klinik für Allgemeine Chirurgie und Thoraxchirurgie, Kiel, Germany
6 Technische Universität München, Klinikum rechts der Isar, Institut für Medizinische Statistik und Epidemiologie, München, Germany
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