Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Oncogene ; 35(34): 4540-8, 2016 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-26804173

RESUMO

Epithelial ovarian cancer (EOC) invasion and metastasis are complex phenomena that result from the coordinated action of many metastatic regulators and must be overcome to improve clinical outcomes for patients with these cancers. The identification of novel therapeutic targets is critical because of the limited success of current treatment regimens, particularly in advanced-stage ovarian cancers. In this study, we found that tetraspanin 8 (TSPAN8) is overexpressed in about 52% (14/27) of EOC tissues and correlates with poor survival. Using small interfering RNA-mediated TSPAN8 knockdown and a competition assay with purified TSPAN8 large extracellular loop (TSPAN8-LEL) protein, we identified TSPAN8-LEL as a key regulator of EOC cell invasion. Furthermore, monotherapy with TSPAN8-blocking antibody we developed shows that antibody-based modulation of TSPAN8-LEL can significantly reduce the incidence of EOC metastasis without severe toxicity in vivo. Finally, we demonstrated that the TSPAN8-blocking antibody promotes the internalization and concomitant downregulation of cell surface TSPAN8. Collectively, our data suggest TSPAN8 as a potential novel therapeutic target in EOCs and antibody targeting of TSPAN8 as an effective strategy for inhibiting invasion and metastasis of TSPAN8-expressing EOCs.


Assuntos
Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Tetraspaninas/antagonistas & inibidores , Anticorpos/farmacologia , Anticorpos/uso terapêutico , Carcinoma Epitelial do Ovário , Feminino , Humanos , Imunoglobulina G/farmacologia , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Tetraspaninas/análise
2.
Oncogene ; 32(48): 5449-57, 2013 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-23644659

RESUMO

It has been suggested that clec14a may be involved in tumor angiogenesis. However, a molecular mechanism has not been clearly identified. In this study, we show for the first time that C-type lectin-like domain (CTLD) of clec14a may be important for regulating cell migration and filopodia formation. Using phage display technology, recombinant human antibodies specific to the CTLDs of human and mouse clec14a (clec14a-CTLD (immunoglobulin G) IgG) were selected. Functional assays using the antibodies showed that clec14a-CTLD IgGs specifically blocked endothelial cell migration and tube formation without affecting cell viability or activation. Further, clec14a-CTLD IgGs inhibited clec14a-mediated cell-cell contact by blocking interaction between CTLDs. Finally, clec14a cross-linking by the clec14a-CTLD IgGs significantly downregulated clec14a expression on the surface of endothelial cells. These results strongly suggest that the clec14a-CTLD may be a key domain in angiogenesis, and that clec14a-CTLD IgGs specifically inhibit angiogenesis by modulating CTLD-mediated cell interactions and clec14a expression on the surface of endothelial cells.


Assuntos
Moléculas de Adesão Celular/química , Moléculas de Adesão Celular/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Imunoglobulina G/imunologia , Lectinas Tipo C/química , Lectinas Tipo C/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Neovascularização Patológica/metabolismo , Animais , Especificidade de Anticorpos , Biomarcadores Tumorais/química , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Moléculas de Adesão Celular/antagonistas & inibidores , Moléculas de Adesão Celular/imunologia , Comunicação Celular , Movimento Celular , Sobrevivência Celular , Regulação para Baixo , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Imunoglobulina G/química , Lectinas Tipo C/antagonistas & inibidores , Lectinas Tipo C/imunologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/imunologia , Camundongos , Estrutura Terciária de Proteína , Pseudópodes/metabolismo , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...