Selectin ligand sialyl-Lewis x antigen drives metastasis of hormone-dependent breast cancers.

Julien, Sylvain; Ivetic, Aleksandar; Grigoriadis, Anita; QiZe, Ding; Burford, Brian; Sproviero, Daisy; Picco, Gianfranco; Gillett, Cheryl; Papp, Suzanne L; Schaffer, Lana; Tutt, Andrew; Taylor-Papadimitriou, Joyce; Pinder, Sarah E; Burchell, Joy M

Julien, Sylvain; Ivetic, Aleksandar; Grigoriadis, Anita; QiZe, Ding; Burford, Brian; Sproviero, Daisy; Picco, Gianfranco; Gillett, Cheryl; Papp, Suzanne L; Schaffer, Lana; Tutt, Andrew; Taylor-Papadimitriou, Joyce; Pinder, Sarah E; Burchell, Joy M.

Afiliación

Julien S; Breast Cancer Biology, King's College London, Guy's Hospital, London, United Kingdom.

Cancer Res ; 71(24): 7683-93, 2011 Dec 15.

Article en En | MEDLINE | ID: mdl-22025563

RESUMEN

The glycome acts as an essential interface between cells and the surrounding microenvironment. However, changes in glycosylation occur in nearly all breast cancers, which can alter this interaction. Here, we report that profiles of glycosylation vary between ER-positive and ER-negative breast cancers. We found that genes involved in the synthesis of sialyl-Lewis x (sLe(x); FUT3, FUT4, and ST3GAL6) are significantly increased in estrogen receptor alpha-negative (ER-negative) tumors compared with ER-positive ones. SLe(x) expression had no influence on the survival of patients whether they had ER-negative or ER-positive tumors. However, high expression of sLe(x) in ER-positive tumors was correlated with metastasis to the bone where sLe(x) receptor E-selectin is constitutively expressed. The ER-positive ZR-75-1 and the ER-negative BT20 cell lines both express sLe(x) but only ZR-75-1 cells could adhere to activated endothelial cells under dynamic flow conditions in a sLe(x) and E-selectin-dependent manner. Moreover, L/P-selectins bound strongly to ER-negative MDA-MB-231 and BT-20 cell lines in a heparan sulfate (HS)-dependent manner that was independent of sLe(x) expression. Expression of glycosylation genes involved in heparan biosynthesis (EXT1 and HS3ST1) was increased in ER-negative tumors. Taken together, our results suggest that the context of sLe(x) expression is important in determining its functional significance and that selectins may promote metastasis in breast cancer through protein-associated sLe(x) and HS glycosaminoglycans.

Asunto(s)

Neoplasias de la Mama/metabolismo; Selectina E/metabolismo; Antígeno Lewis X/metabolismo; Neoplasias Hormono-Dependientes/metabolismo; Western Blotting; Neoplasias de la Mama/genética; Neoplasias de la Mama/patología; Adhesión Celular; Línea Celular; Línea Celular Tumoral; Selectina E/genética; Femenino; Fucosiltransferasas/genética; Fucosiltransferasas/metabolismo; Perfilación de la Expresión Génica; Regulación Neoplásica de la Expresión Génica; Glicómica/métodos; Heparitina Sulfato/metabolismo; Células Endoteliales de la Vena Umbilical Humana/citología; Células Endoteliales de la Vena Umbilical Humana/metabolismo; Humanos; Antígeno Lewis X/genética; N-Acetilglucosaminiltransferasas/genética; N-Acetilglucosaminiltransferasas/metabolismo; Metástasis de la Neoplasia; Neoplasias Hormono-Dependientes/genética; Neoplasias Hormono-Dependientes/patología; Análisis de Secuencia por Matrices de Oligonucleótidos; Receptores de Estrógenos/metabolismo; Reacción en Cadena de la Polimerasa de Transcriptasa Inversa; Antígeno Sialil Lewis X; Sialiltransferasas/genética; Sialiltransferasas/metabolismo; Sulfotransferasas/genética; Sulfotransferasas/metabolismo; beta-Galactosida alfa-2,3-Sialiltransferasa

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Antígeno Lewis X / Selectina E / Neoplasias Hormono-Dependientes Idioma: En Revista: Cancer Res Año: 2011 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos

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