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Heparan sulfate proteoglycans as trastuzumab targets in anoikis-resistant endothelial cells

Jessica Oyie Sousa Onyeisi1, Paulo Castanho de Almeida Pernambuco Filho2, Silvana de Araujo Lopes2

  • 1Disciplina de Biologia Molecular, Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, Brazil.

Journal of Cellular Biochemistry
|April 5, 2019
PubMed

Insights

Trastuzumab treatment reduces invasion and proliferation in anoikis-resistant endothelial cells by altering heparan sulfate proteoglycans (HSPGs) and glycosaminoglycans (GAGs). This impacts cancer progression and metastasis.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Biochemistry

Background:

  • Anoikis resistance is crucial for cancer cell metastasis.
  • Trastuzumab is a cancer therapeutic, but its precise molecular targets remain unclear.
  • Heparan sulfate proteoglycans (HSPGs) and glycosaminoglycans (GAGs) influence tumor development and drug response.

Purpose of the Study:

  • To investigate the effects of trastuzumab on HSPGs and sulfated glycosaminoglycans (SGAGs) in anoikis-resistant endothelial cells.
  • To elucidate trastuzumab's mechanism of action in the context of anoikis resistance.

Main Methods:

  • Treatment of anoikis-resistant endothelial cells with trastuzumab.
  • Assessment of cell adhesion, invasion, proliferation, and angiogenic capacity.
  • Cell cycle analysis.
  • Quantification of HSPGs, SGAGs, and heparan sulfate biosynthesis.

Main Results:

  • Trastuzumab increased fibronectin adhesion and decreased invasion, proliferation, and angiogenesis.
  • A significant increase in S-phase cells was observed.
  • Trastuzumab reduced syndecan-4 and perlecan expression and heparan sulfate biosynthesis.

Conclusions:

  • Trastuzumab interacts with cell surface and ECM GAGs and proteoglycans.
  • This interaction modulates cellular events in anoikis-resistant endothelial cells, potentially impacting cancer progression.
Keywords:
anoikiscancerheparan sulfate proteoglycanssulfated glycosaminoglycanstrastuzumab

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