Tumor metastasis-associated heparanase (heparan sulfate endoglycosidase) activity in human melanoma cells |
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| Authors: | M Nakajima T Irimura G L Nicolson |
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| Affiliation: | 1. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States of America;2. Kaiser Permanente, Northern California, United States of America;3. Dana-Farber Cancer Institute, Boston, MA, United States of America;4. US Oncology Network, The Woodlands, TX, United States of America;5. University of Cincinnati Cancer Center, Cincinnati, OH, United States of America;6. Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ, United States of America;7. Aravive, Inc., Houston, TX, United States of America;8. Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America;1. Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA;2. Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA;3. Department of Dermatology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA;4. Department of Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA;5. Penn State Melanoma and Skin Cancer Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA;6. Penn State Melanoma Therapeutics Program, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA;7. Foreman Foundation for Melanoma Research, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA |
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| Abstract: | We discovered previously a tumor metastasis-associated heparan sulfate (HS)-degrading endoglycosidase in mouse melanoma cells that is a unique endo-beta-glucuronidase (heparanase) capable of specifically cleaving HS at intrachain sites (Nakajima et al., J. Biol. Chem., 259 (1984) 2283. Using unmodified- and chemically modified-HS and heparin substrates we demonstrate that human Hs939 and mouse B16 melanoma cells possess a HS-degrading endoglycosidase of similar specificity. Melanoma heparanase showed high activity against N-desulfated N-acetylated HS, and we therefore synthesized a solid-phase heparanase substrate crosslinking partially N-desulfated N-[14C] acetylated HS to agarose gel beads via one covalent linkage. Using this solid-phase substrate 15 human malignant melanoma cell lines were assayed for heparanase activity. All of the melanoma cells tested had heparanase activity, and almost all possessed activities comparable or greater than that of the murine B16-F1 melanoma line. Human A375 melanoma variants of high lung metastatic potential in athymic nude mice had significantly higher heparanase activities than did A375 parental cells of low metastatic potential. |
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