4.7 Review

Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management

Journal

BIOMOLECULES
Volume 11, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/biom11020136

Keywords

biomarker; cancer; cancer therapy; extracellular vesicles; glycosaminoglycans; heparan sulfate; proteoglycans

Funding

  1. FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020
  2. FCT-Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Inovacao [POCI-01-0145-FEDER-007274]
  3. FCT [SFRH/BD/137319/2018, 2020.06412.BD, POCI-01-0145-FEDER-028489]
  4. COST Action [CA18103 INNOGLY]
  5. Fundação para a Ciência e a Tecnologia [2020.06412.BD, SFRH/BD/137319/2018] Funding Source: FCT

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Heparan sulfate (HS) plays a crucial role in cancer development, impacting various aspects such as proliferation, angiogenesis, and metastasis. Due to its interaction with different ligands, HS has pleiotropic effects on important cellular receptors and downstream signaling pathways. Aberrant expression of HS can determine malignant features of tumors.
In an era when cancer glycobiology research is exponentially growing, we are witnessing a progressive translation of the major scientific findings to the clinical practice with the overarching aim of improving cancer patients' management. Many mechanistic cell biology studies have demonstrated that heparan sulfate (HS) glycosaminoglycans are key molecules responsible for several molecular and biochemical processes, impacting extracellular matrix properties and cellular functions. HS can interact with a myriad of different ligands, and therefore, hold a pleiotropic role in regulating the activity of important cellular receptors and downstream signalling pathways. The aberrant expression of HS glycan chains in tumours determines main malignant features, such as cancer cell proliferation, angiogenesis, invasion and metastasis. In this review, we devote particular attention to HS biological activities, its expression profile and modulation in cancer. Moreover, we highlight HS clinical potential to improve both diagnosis and prognosis of cancer, either as HS-based biomarkers or as therapeutic targets.

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