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Heparan sulfate proteoglycans as trastuzumab targets in anoikis-resistant endothelial cells.
Heparan sulfate proteoglycans as trastuzumab targets in anoikis-resistant endothelial cells.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 2019 Aug; Vol. 120 (8), pp. 13826-13840. Date of Electronic Publication: 2019 Apr 04. - Publication Year :
- 2019
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Abstract
- 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.<br /> (© 2019 Wiley Periodicals, Inc.)
- Subjects :
- Angiogenesis Inhibitors pharmacology
Animals
Cell Adhesion drug effects
Cell Cycle drug effects
Cell Line
Cell Proliferation drug effects
Cell Survival drug effects
Chondroitin Sulfates metabolism
Endothelial Cells drug effects
Gene Expression Regulation drug effects
Heparitin Sulfate metabolism
Rabbits
Anoikis drug effects
Endothelial Cells metabolism
Heparan Sulfate Proteoglycans metabolism
Trastuzumab pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4644
- Volume :
- 120
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30945340
- Full Text :
- https://doi.org/10.1002/jcb.28656