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

Anoikis is a form of programmed cell death induced by loss of contact from neighboring cells or from their extracellular matrix (ECM). Many tumorigenic cells are anoikis resistant, facilitating cancer progression and metastasis. Trastuzumab is a monoclonal antibody used for the treatment of breast a...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2019-08, Vol.120 (8), p.13826-13840
Main Authors: Onyeisi, Jessica Oyie Sousa, Castanho de Almeida Pernambuco Filho, Paulo, Araujo Lopes, Silvana, Nader, Helena Bonciani, Lopes, Carla Cristina
Format: Article
Language:English
Subjects:
Angiogenesis
Anoikis
Apoptosis
Biosynthesis
Breast cancer
Cancer
Cell cycle
Cell death
Cell surface
Drug development
Endothelial cells
Extracellular matrix
Fibronectin
Glycosaminoglycans
Heparan sulfate
Heparan sulfate proteoglycans
Immunotherapy
Metastases
Monoclonal antibodies
Perlecan
Proteoglycans
S phase
Sulfate resistance
sulfated glycosaminoglycans
Sulfates
Syndecan
Targeted cancer therapy
Trastuzumab
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Summary:Anoikis is a form of programmed cell death induced by loss of contact from neighboring cells or from their extracellular matrix (ECM). Many tumorigenic cells are anoikis resistant, facilitating cancer progression and metastasis. Trastuzumab is a monoclonal antibody used for the treatment of breast and gastric cell cancer, but its mechanism of action is not well elucidated and its target molecules not well defined. Heparan sulfate proteoglycans (HSPGs) and glycosaminoglycans (GAGs) play important roles in tumor development and in response of cancer cells to drugs. This study investigates the effect of trastuzumab on the expression of HSPGs and sulfated glycosaminoglycans (SGAGs) in anoikis‐resistant endothelial cells. After trastuzumab treatment, endothelial cells resistant to anoikis show an increase in adhesion to fibronectin followed by a decrease in invasion, proliferation, and angiogenic capacity. In addition, a significant increase in the number of cells in the S phase of the cell cycle was also observed. In relation to HSPGs and SGAGs expression, we observed a decrease in syndecan‐4 and perlecan expression, as well as in the heparan sulfate biosynthesis in anoikis‐resistant endothelial cells after exposure to trastuzumab. Our results suggest that trastuzumab interacts with GAGs and proteoglycans of the cell surface and ECM and through this interaction controls cellular events in anoikis‐resistant endothelial cells. Heparan sulfate proteoglycans (HSPGs) and glycosaminoglycans (GAGs) play important roles in tumor development and in response of cancer cells to drugs. This study investigates the effect of trastuzumab on the expression of HSPGs and sulfated glycosaminoglycans (SGAGs) in anoikis‐resistant endothelial cells. Our results suggest that trastuzumab interacts with GAGs and proteoglycans of the cell surface and extracellular matrix (ECM) and through this interaction controls cellular events in anoikis‐resistant endothelial cells.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.28656