This Article Full Text Full Text (PDF) Supplemental Material Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Galle, J. Articles by Aust, G. Search for Related Content PubMed PubMed Citation Articles by Galle, J. Articles by Aust, G.

(American Journal of Pathology. 2006;169:1802-1811.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060006

Individual Cell-Based Models of Tumor-Environment Interactions

Multiple Effects of CD97 on Tumor Invasion

Joerg Galle^*, Doreen Sittig, Isabelle Hanisch, Manja Wobus, Elke Wandel, Markus Loeffler^* and Gabriela Aust

From the Interdisciplinary Center for Bioinformatics,^* the Institute for Medical Informatics, Statistics, and Epidemiology, the Center of Surgery, Research Laboratories, and the Interdisciplinary Center of Clinical Research, University of Leipzig, Leipzig, Germany

The presence of scattered tumor cells at the invading front of several carcinomas has clinical significance. These cells differ in their protein expression from cells in central tumor regions as recently shown for the EGF-TM7 receptor CD97. To understand the impact of such heterogeneity on tumor invasion, we investigated tumor cells with modified CD97 expression in vitro and in vivo. Applying an individual cell-based computer model approach, we linked specific cell properties of these cells to tumor invasion characteristics. CD97 overexpression promoted tumor growth in scid mice, stimulated single cell motility, increased proteolytic activity of matrix metalloproteinases, and secretion of chemokines in vitro in an isoform-specific manner. We demonstrated by computer simulation studies that these effects of CD97 can increase the invasion capacity of tumors. Furthermore, they can cause the appearance of scattered tumor cells at the invasion front. We identified local tumor environment interactions as triggers of these multiple capabilities. Experimentally, our simulation results are supported by the finding that CD97 expression in tumor cells is regulated by their environment. Our combined experimental-theoretical analysis provides novel insight to how variations of individual cell properties can be linked to individual patterns of tumor cell invasion.

This article has been cited by other articles:

				S. Yona, H.-H. Lin, P. Dri, J. Q. Davies, R. P. G. Hayhoe, S. M. Lewis, S. E. M. Heinsbroek, K. A. Brown, M. Perretti, J. Hamann, et al. Ligation of the adhesion-GPCR EMR2 regulates human neutrophil function FASEB J, March 1, 2008; 22(3): 741 - 751. [Abstract] [Full Text] [PDF]