HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 WARTENBERG, M. Articles by SAUER, H. Search for Related Content PubMed PubMed Citation Articles by WARTENBERG, M. Articles by SAUER, H.

Tumor-induced angiogenesis studied in confrontation cultures of multicellular tumor spheroids and embryoid bodies grown from pluripotent embryonic stem cells

Department of Neurophysiology, University of Cologne, D-50931 Cologne, Germany; and
^* Max-Planck-Institute of Molecular Physiology, D-44227 Dortmund, Germany

¹Correspondence: Department of Neurophysiology, Robert-Koch-Str. 39, D-50931 Cologne, Germany. E-mail: hs{at}physiologie.uni-koeln.de

Tumor vascularization is the rate-limiting step for the progression of cancer. Differential steps of tumor-induced angiogenesis were studied by a novel in vitro confrontation culture of avascular multicellular prostate tumor spheroids and embryoid bodies grown from pluripotent embryonic stem (ES) cells. Vascularization in embryoid bodies started on day 5 of cell culture and was paralleled by down-regulation of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF). In parallel, a dissipation of gradients in the pericellular oxygen pressure was observed as measured by O₂-sensitive microelectrodes. After 24–48 h of confrontation culture, cells positive for platelet endothelial cell adhesion molecule (PECAM-1) became visible in the contact region between the embryoid body and the tumor spheroid and sprouted within the confrontation cultures during subsequent days. Tumor-induced angiogenesis resulted in growth stimulation of tumor spheroids, disappearance of central necrosis and a reduction of the pericellular oxygen pressure. Furthermore, tumor vascularization resulted in elevated levels of HIF-1, VEGF, heat shock protein 27 (HSP27), and P-glycoprotein. Tumor-induced angiogenesis may augment the oxygen consumption in tumors resulting in an increased expression of hypoxia-related, proangiogenic genes as well as of HSP27 and P-glycoprotein, which are involved in a multidrug resistance phenotype.—Wartenberg, M., Dönmez, F., Ling, F. C., Acker, H., Hescheler, J., Sauer, H. Tumor-induced angiogenesis studied in confrontation cultures of multicellular tumor spheroids and embryoid bodies grown from pluripotent embryonic stem cells.

Key Words: VEGF • hypoxia • multidrug resistance • P-glycoprotein • HSP27

This article has been cited by other articles:

				M. Schmelter, B. Ateghang, S. Helmig, M. Wartenberg, and H. Sauer Embryonic stem cells utilize reactive oxygen species as transducers of mechanical strain-induced cardiovascular differentiation FASEB J, June 1, 2006; 20(8): 1182 - 1184. [Abstract] [Full Text] [PDF]

				B. Ateghang, M. Wartenberg, M. Gassmann, and H. Sauer Regulation of cardiotrophin-1 expression in mouse embryonic stem cells by HIF-1{alpha} and intracellular reactive oxygen species J. Cell Sci., March 15, 2006; 119(6): 1043 - 1052. [Abstract] [Full Text] [PDF]

				K. Baar New dimensions in tissue engineering: possible models for human physiology Exp Physiol, November 1, 2005; 90(6): 799 - 806. [Abstract] [Full Text] [PDF]

				L. A. Kunz-Schughart, J. P. Freyer, F. Hofstaedter, and R. Ebner The Use of 3-D Cultures for High-Throughput Screening: The Multicellular Spheroid Model J Biomol Screen, June 1, 2004; 9(4): 273 - 285. [Abstract] [PDF]

				W. E. G. Muller, N. L. Thakur, H. Ushijima, A. N. Thakur, A. Krasko, G. Le Pennec, M. M. Indap, S. Perovic-Ottstadt, H. C. Schroder, G. Lang, et al. Matrix-mediated canal formation in primmorphs from the sponge Suberites domuncula involves the expression of a CD36 receptor-ligand system J. Cell Sci., May 15, 2004; 117(12): 2579 - 2590. [Abstract] [Full Text] [PDF]

				P. Wachsberger, R. Burd, and A. P. Dicker Tumor Response to Ionizing Radiation Combined with Antiangiogenesis or Vascular Targeting Agents: Exploring Mechanisms of Interaction Clin. Cancer Res., June 1, 2003; 9(6): 1957 - 1971. [Abstract] [Full Text] [PDF]

				K. M. Comerford, T. J. Wallace, J. Karhausen, N. A. Louis, M. C. Montalto, and S. P. Colgan Hypoxia-inducible Factor-1-dependent Regulation of the Multidrug Resistance (MDR1) Gene Cancer Res., June 1, 2002; 62(12): 3387 - 3394. [Abstract] [Full Text] [PDF]