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Proteoglycans and tumor progression: Janus-faced molecules with contradictory functions in cancer

József Tímár1, Károly Lapis, József Dudás

  • 1Department of Tumor Progression, National Institute of Oncology, Budapest, Hungary. jtimar@oncol.hu

Seminars in Cancer Biology
|June 27, 2002
PubMed

Insights

Proteoglycans (PG) play a dual role in tumor spread, with altered gene expression and glycosaminoglycan (GAG) modifications influencing cancer progression. Targeting cell surface heparan sulfate (HS) proteoglycans (HSPG) offers a potential anti-metastatic strategy.

Area of Science:

  • Molecular biology
  • Cancer research
  • Biochemistry

Background:

  • Tumor dissemination involves complex molecular mechanisms.
  • Proteoglycans (PG) are implicated in tumor progression but exhibit dual roles.
  • Alterations in PG core protein expression and glycosaminoglycan (GAG) side chains are observed in cancers.

Purpose of the Study:

  • To elucidate the Janus-faced role of proteoglycans in tumor dissemination.
  • To investigate the impact of altered PG expression and GAG modifications on cancer progression.
  • To identify potential therapeutic targets for anti-metastatic interventions.

Main Methods:

  • Analysis of proteoglycan gene expression patterns in tumors.
  • Characterization of glycosaminoglycan (GAG) modifications in proteoglycans.
  • Evaluation of specific proteoglycans (decorin, perlecan) in tumor progression.
  • Identification of cell surface heparan sulfate proteoglycan (HSPG) groups involved in metastasis.

Main Results:

  • Tumor progression is associated with either loss or neoexpression of surface PGs.
  • Hybrid PGs with chondroitin and heparan sulfate GAGs show altered functions.
  • Decorin inhibits, while perlecan promotes tumor progression.
  • Metastatic tumor cells require specific cell surface HSPG species (syndecan, glypican, CD44v3).
  • Heparan sulfate (HS) chains on HSPGs contain molecular signatures influencing metastasis.

Conclusions:

  • Proteoglycan alterations, including GAG modifications, are critical in tumor dissemination.
  • Specific cell surface HSPGs and their HS-chain structures are essential for metastasis.
  • Tumor cell surface heparan sulfate (PG) presents a promising target for anti-metastatic therapies.

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