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Tumor-endothelial interaction links the CD44(+)/CD24(-) phenotype with poor prognosis in early-stage breast cancer

Buess, Martin and Rajski, Michal and Vogel-Durrer, Brigitte M. L. and Herrmann, Richard and Rochlitz, Christoph. (2009) Tumor-endothelial interaction links the CD44(+)/CD24(-) phenotype with poor prognosis in early-stage breast cancer. Neoplasia, Vol. 11. S. 987-1002.

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Official URL: http://edoc.unibas.ch/dok/A6003727

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Abstract

MATERIALS AND METHODS: The genomic effects of tumor-endothelial interactions in cancer are not yet well characterized. To study this interaction in breast cancer, we set up an ex vivo coculture model with human benign and malignant breast epithelial cells with endothelial cells to determine the associated gene expression changes using DNA microarrays. RESULTS: The most prominent response to coculture was the induction of the M-phase cell cycle genes in a subset of breast cancer cocultures that were absent in cocultures with normal breast epithelial cells. In monoculture, tumor cells that contained the stem cell-like CD44(+)/CD24(-) signature had a lower expression of the M-phase cell cycle genes than the CD44(-)/CD24(+) cells, and in the CD44(+)/CD24(-) cocultures, these genes were induced. Pretreatment gene expression profiles of early-stage breast cancers allowed evaluating in vitro effects in vivo. The expression of the gene set derived from the coculture provided a basis for the segregation of the tumors into two groups. In a univariate analysis, early-stage tumors with high expression levels (n = 137) of the M-phase cell cycle genes had a significantly lower metastasis-free survival rate (P = 1.8e - 5, 50% at 10 years) and overall survival rate (P = 5e - 9, 52% at 10 years) than tumors with low expression (n = 158; metastasis-free survival, 73%; overall survival, 84%). CONCLUSIONS: Our results suggest that the interaction of endothelial cells with tumor cells that express the CD44(+)/CD24(-) signature, which indicates a low proliferative potential, might explain the unexpected and paradoxical association of the CD44(+)/CD24(-) signature with highly proliferative tumors that have an unfavorable prognosis.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Onkologie (Herrmann)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Onkologie (Herrmann)
UniBasel Contributors:Rochlitz, Christoph and Herrmann, Richard and Buess, Martin
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Stockton Press
ISSN:1522-8002
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:12
Deposited On:26 Apr 2013 06:59

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