A newly generated functional antibody identifies Tn antigen as a novel determinant in the cancer cell-lymphatic endothelium interaction.
Glycobiology
; 19(10): 1056-67, 2009 Oct.
Article
en En
| MEDLINE
| ID: mdl-19528665
ABSTRACT
Malignant transformation of epithelial cells is frequently associated with the alteration of glycosylation pathways. Tn is a common tumor-associated carbohydrate antigen present in 90% of human carcinomas and its expression correlates with metastatic potential and poor prognosis. Despite its relevance, the functional role of Tn in tumor biology has not been firmly established probably for the lack of appropriate experimental tools. Our aims were to produce highly reactive monoclonal antibodies against Tn making use of synthetically produced Tn and to test their usefulness for in vivo imaging as well as to define their potential functional activity in tumor cell spread. We immunized mice with Tn clustered on cationized BSA and screened the positive hybridomas with Tn-biotinylated alginate. Enzyme-linked immuno sorbent assay and immunofluorescence assays revealed that the most reactive anti-Tn IgM mAb (2154F12A4) selectively recognized Tn on the MCF7 breast cancer cell line since its binding to the cell membrane was completely abolished by preincubation with purified Tn. Importantly, QDot 800-conjugated mAb injected in MCF7-tumor bearing mice specifically bound to primary tumor lesions as well as to metastases in lymph nodes. In addition, this mAb was able to inhibit cancer cell adhesion to lymphatic endothelium suggesting a novel involvement of Tn in the lymphatic dissemination of cancer cells and hypothesizing future applications in inhibiting lymphatic metastases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antígenos de Carbohidratos Asociados a Tumores
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Ganglios Linfáticos
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Anticuerpos Monoclonales
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Anticuerpos Antineoplásicos
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Neoplasias
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Glycobiology
Asunto de la revista:
BIOQUIMICA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Italia