Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis.
Proc Natl Acad Sci U S A
; 110(13): 5052-7, 2013 Mar 26.
Article
en En
| MEDLINE
| ID: mdl-23479624
ABSTRACT
Cancer metastasis and immune suppression are critical issues in cancer therapy. Here, we show that a ß-galactoside-binding lectin [galectin-3 (gal3)] that recognizes the Thomsen-Friedenreich disaccharide (TFD, Galß1,3GalNAc) present on the surface of most cancer cells is involved in promoting angiogenesis, tumor-endothelial cell adhesion, and metastasis of prostate cancer cells, as well as evading immune surveillance through killing of activated T cells. To block gal3-mediated interactions, we purified a glycopeptide from cod (designated TFD100) that binds gal3 with picomolar affinity. TFD100 blocks gal3-mediated angiogenesis, tumor-endothelial cell interactions, and metastasis of prostate cancer cells in mice at nanomolar levels. Moreover, apoptosis of activated T cells induced by either recombinant gal3 or prostate cancer patient serum-associated gal3 was inhibited at nanomolar concentration of TFD100. Because the gal3-TFD interaction is a key factor driving metastasis in most epithelial cancers, this high-affinity TFD100 should be a promising antimetastatic agent for the treatment of various cancers, including prostate adenocarcinoma.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Linfocitos T
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Adenocarcinoma
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Apoptosis
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Proteínas Anticongelantes
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Proteínas de Peces
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Galectina 3
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Gadus morhua
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Proteínas de Neoplasias
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Antineoplásicos
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos