Magnetic Resonance Imaging Visualization of Hyaluronidase in Ovarian Carcinoma
Open Access
- 15 November 2005
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 65 (22), 10316-10323
- https://doi.org/10.1158/0008-5472.can-04-3947
Abstract
Hyaluronan, a high molecular weight, negatively charged polysaccharide, is a major constituent of the extracellular matrix. High molecular weight hyaluronan is antiangiogenic, but its degradation by hyaluronidase generates proangiogenic breakdown products. Thus, by expression of hyaluronidase, cancer cells can tilt the angiogenic balance of their microenvironment. Indeed, hyaluronidase-mediated breakdown of hyaluronan correlates with aggressiveness and invasiveness of ovarian cancer metastasis and with tumor angiogenesis. The goal of this work was to develop a novel smart contrast material for detection of hyaluronidase activity by magnetic resonance imaging (MRI). Gadolinium-diethylenetriaminepentaacetic acid (GdDTPA) covalently linked to hyaluronan on the surface of agarose beads showed attenuated relaxivity. Hyaluronidase, either purified from bovine testes or secreted by ES-2 and OVCAR-3 human epithelial ovarian carcinoma cells, activated the hyaluronan-GdDTPA-beads by rapidly altering the R1 and R2 relaxation rates. The change in relaxation rates was consistent with the different levels of biologically active hyaluronidase secreted by those cells. Hyaluronan-GdDTPA-beads were further used for demonstration of MRI detection of hyaluronidase activity in the proximity of s.c. ES-2 ovarian carcinoma tumors in nude mice. Thus, hyaluronan-GdDTPA-beads could allow noninvasive molecular imaging of hyaluronidase-mediated tilt of the peritumor angiogenic balance.Keywords
This publication has 37 references indexed in Scilit:
- Regulation of hyaluronan expression during cervical ripeningGlycobiology, 2004
- Hyaluronan: from extracellular glue to pericellular cueNature Reviews Cancer, 2004
- Longitudinal MRI tracking of the angiogenic response to hind limb ischemic injury in the mouseMagnetic Resonance in Medicine, 2004
- Devising a pathway for hyaluronan catabolism: are we there yet?Glycobiology, 2003
- Magnetic Sensors for Protease AssaysAngewandte Chemie-International Edition, 2003
- Gonadotropin Stimulation of MLS Human Epithelial Ovarian Carcinoma Cells Augments Cell Adhesion Mediated by CD44 and by αv-IntegrinGynecologic Oncology, 2002
- Evidence That the Serum Inhibitor of Hyaluronidase May Be a Member of the Inter-α-inhibitor FamilyPublished by Elsevier BV ,2000
- Expression Analysis of Six Paralogous Human Hyaluronidase Genes Clustered on Chromosomes 3p21 and 7q31Genomics, 1999
- Antisense Inhibition of Hyaluronan Synthase-2 in Human Articular Chondrocytes Inhibits Proteoglycan Retention and Matrix AssemblyPublished by Elsevier BV ,1999
- The Biological Activity of Hyaluron Sulfuric Acid.Acta Physiologica Scandinavica, 1951