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

Autor(es)

Sousa Onyeisi, Jessica Oyie ^[1] ; de Almeida Pernambuco Filho, Paulo Castanho ^[2] ; Lopes, Silvana deAraujo ^[2] ; Nader, Helena Bonciani ^[1] ; Lopes, Carla Cristina ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Bioquim, Disciplina Biol Mol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Ciencias Biol, Diadema, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Biochemistry; v. 120, n. 8, p. 13826-13840, AUG 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 15/22546-0 - Avaliação funcional dos genes sindecam-4 e PIK3CA (Fosfatidilinositol 4,5-bifosfato 3-quinase, subunidade catalítica alfa) em células endoteliais resistentes ao anoikis
• Beneficiário: Carla Cristina Lopes de Azevedo
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/03964-6 - Glicosaminoglicanos e proteoglicanos: relação estrutura e função
• Beneficiário: Helena Bonciani Nader
• Linha de fomento: Auxílio à Pesquisa - Temático