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Tumor cell surface heparan sulfate as cryptic promoters or inhibitors of tumor growth and metastasis.

Abstract
Heparan sulfate glycosaminoglycans, present at the cell surface and in the extracellular matrix that surrounds cells, are important mediators of complex biological processes. Furthermore, it is now apparent that cells dynamically regulate the structure of their heparan sulfate "coat" to differentially regulate extracellular signals. In the present study, the importance of sequence information contained within tumor cell-surface heparan sulfate was investigated. Herein, we demonstrate that the heparan sulfate glycosaminoglycan coat present on tumor cells contains bioactive sequences that impinge on tumor-cell growth and metastasis. Importantly, we find that growth promoting as well as growth inhibiting sequences are contained within the polysaccharide coat. Furthermore, we find that the dynamic balance between these distinct polysaccharide populations regulates specific intracellular signal-transduction pathways. This study not only provides a framework for the development of polysaccharide-based anti-cancer molecules but also underscores the importance of understanding a cell's polysaccharide array in addition to its protein complement, to understand how genotype translates to phenotype in this post-genomic age.
AuthorsDongfang Liu, Zachary Shriver, Ganesh Venkataraman, Yosuf El Shabrawi, Ram Sasisekharan
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 99 Issue 2 Pg. 568-73 (Jan 22 2002) ISSN: 0027-8424 [Print] United States
PMID11805315 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Growth Inhibitors
  • Growth Substances
  • Heparan Sulfate Proteoglycans
Topics
  • Animals
  • Cell Membrane (physiology)
  • Growth Inhibitors (physiology)
  • Growth Substances (physiology)
  • Heparan Sulfate Proteoglycans (chemistry, pharmacology, physiology)
  • Lung Neoplasms (pathology, physiopathology, secondary)
  • Melanoma, Experimental (pathology, physiopathology)
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental (pathology, physiopathology, secondary)
  • Signal Transduction

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