This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Abramovitch, R. Articles by Neeman, M. Search for Related Content PubMed PubMed Citation Articles by Abramovitch, R. Articles by Neeman, M.

Neovascularization Induced Growth of Implanted C6 Glioma Multicellular Spheroids: Magnetic Resonance Microimaging¹

Department of Hormone Research, Weizmann Institute of Science, Rehovot 76100, Israel

Magnetic resonance imaging has been used to follow noninvasively tumor neovascularization and tumor growth in a model system of multicellular C6 rat glioma spheroids implanted s.c. in nude mice. By positioning a single spheroid approximately 1 cm from the site of incision both the vascularization of the tumor and the wound healing processes were spatially separated and could be simultaneously followed. The model proposed here provides defined initial conditions of tumor geometry and cell proliferative status and separation of initial tumor growth from neovascularization. Magnetic susceptibility relaxation provided an intrinsic marker for blood containing vessels. The implanted spheroid induced vessel growth within 4 days after implantation that was geometrically oriented toward the spheroid and distinct from wound healing at the site of incision. Volume measurements showed a corresponding 4-day lag in growth followed by Gompertz progression. Sham implantation of agarose beads of similar diameter showed no induction of vessel growth, ruling out a direct effect of wound healing. The new vessels penetrating the tumor were highly permeable to the contrast reagent gadolinium-diethylenetri-aminepentaacetic acid. This permeability may be due to the action of vascular endothelial growth factor, a major angiogenic growth factor in this system, and a potent permeability factor.

¹ This work was supported by Research Grant 93-00073 from The United States-Israel Binational Science Foundation. M. N. is the incumbent Dr. Phil Gold Career Development Chair in Cancer Research.

² To whom requests for reprints should be addressed.

Received 12/ 1/94. Accepted 2/27/95.

This article has been cited by other articles:

				G. A. Christoforidis, A. Kangarlu, A. M. Abduljalil, P. Schmalbrock, A. Chaudhry, A. Yates, and D. W. Chakeres Susceptibility-Based Imaging of Glioblastoma Microvascularity at 8 T: Correlation of MR Imaging and Postmortem Pathology AJNR Am. J. Neuroradiol., May 1, 2004; 25(5): 756 - 760. [Abstract] [Full Text] [PDF]

				G. A. Christoforidis, J. C. Grecula, H. B. Newton, A. Kangarlu, A. M. Abduljalil, P. Schmalbrock, and D. W Chakeres Visualization of Microvascularity in Glioblastoma Multiforme With 8-T High-Spatial-Resolution MR Imaging AJNR Am. J. Neuroradiol., October 1, 2002; 23(9): 1553 - 1556. [Abstract] [Full Text] [PDF]

				W. Yang, S. Arii, A. Mori, K. Furumoto, T. Nakao, N. Isobe, T. Murata, H. Onodera, and M. Imamura sFlt-1 Gene-transfected Fibroblasts: A Wound-specific Gene Therapy Inhibits Local Cancer Recurrence Cancer Res., November 1, 2001; 61(21): 7840 - 7845. [Abstract] [Full Text] [PDF]

				M. Shaharabany, R. Abramovitch, T. Kushnir, G. Tsarfaty, M. Ravid-Megido, J. Horev, R. Ron, Y. Itzchak, and I. Tsarfaty In Vivo Molecular Imaging of Met Tyrosine Kinase Growth Factor Receptor Activity in Normal Organs and Breast Tumors Cancer Res., June 1, 2001; 61(12): 4873 - 4878. [Abstract] [Full Text] [PDF]

				N. W. Bengtson and D. I. H. Linzer Inhibition of Tumor Growth by the Antiangiogenic Placental Hormone, Proliferin-Related Protein Mol. Endocrinol., December 1, 2000; 14(12): 1934 - 1943. [Abstract] [Full Text]

				P. Carmeliet, L. Moons, and D. Collen Mouse models of angiogenesis, arterial stenosis, atherosclerosis and hemostasis Cardiovasc Res, July 1, 1998; 39(1): 8 - 33. [Abstract] [Full Text] [PDF]

				Y. S. Schiffenbauer, R. Abramovitch, G. Meir, N. Nevo, M. Holzinger, A. Itin, E. Keshet, and M. Neeman Loss of ovarian function promotes angiogenesis in human ovarian carcinoma PNAS, November 25, 1997; 94(24): 13203 - 13208. [Abstract] [Full Text] [PDF]

				W. Mueller-Klieser Three-dimensional cell cultures: from molecular mechanisms to clinical applications Am J Physiol Cell Physiol, October 1, 1997; 273(4): C1109 - C1123. [Abstract] [Full Text] [PDF]