Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 120, Issue 8, Pages 13826-13840Publisher
WILEY
DOI: 10.1002/jcb.28656
Keywords
anoikis; cancer; heparan sulfate proteoglycans; sulfated glycosaminoglycans; trastuzumab
Categories
Funding
- Financiadora de Estudos e Projetos
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2015/22546-0, 2015/03964-6]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [15/22546-0] Funding Source: FAPESP
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available