Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast cancer
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Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast cancer. / Dwek, M V; Ross, H A; Streets, A J; Brooks, S A; Adam, E; Titcomb, A; Woodside, J V; Schumacher, U; Leathem, A J.
in: INT J CANCER, Jahrgang 95, Nr. 2, 20.03.2001, S. 79-85.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast cancer
AU - Dwek, M V
AU - Ross, H A
AU - Streets, A J
AU - Brooks, S A
AU - Adam, E
AU - Titcomb, A
AU - Woodside, J V
AU - Schumacher, U
AU - Leathem, A J
N1 - Copyright 2001 Wiley-Liss, Inc.
PY - 2001/3/20
Y1 - 2001/3/20
N2 - Predicting long-term outcome after breast-cancer diagnosis remains problematic, particularly for patients with clinically small, axillary lymph node- negative tumours. Evidence suggests that the lectin Helix pomatia agglutinin (HPA) identifies oligosaccharides associated with poor-prognosis cancer. Our aim was to identify oligosaccharides that bind HPA in aggressive breast cancers. Breast-cancer cell lines (MCF-7, BT-549 and BT-20) and a cell line from human milk (HBL-100), which showed a range of HPA-binding intensities, were used to extract HPA-binding glycoproteins. Oligosaccharides were released using anhydrous hydrazine and separated on a range of HPLC matrices. We investigated whether HPA-binding oligosaccharides from cell lines were present in human breast-cancer tissues, using 69 breast-cancer specimens from patients with between 5 and 10 years' follow-up. A monosialylated oligosaccharide was over-expressed in the cell line that bound HPA strongly. Further analysis by normal-phase HPLC showed that the 2-aminobenzamide-conjugated oligosaccharide had a hydrodynamic volume of 4.58 glucose units (HPAgly1). Increased expression of HPAgly1 was associated with HPA staining of breast-cancer specimens (Student's t-test p = 0.025). Analysis of oligosaccharide levels and disease-free survival after treatment for breast cancer indicated a shorter disease-free interval for patients with elevated levels of HPAgly1. This is the first time that histochemical lectin staining has been correlated with biochemical mapping of oligosaccharides. Using this approach, we have identified a monosialylated HPA lectin-binding oligosaccharide present in breast-cancer cells grown in vitro which is elevated in breast-cancer specimens that bind the lectin.
AB - Predicting long-term outcome after breast-cancer diagnosis remains problematic, particularly for patients with clinically small, axillary lymph node- negative tumours. Evidence suggests that the lectin Helix pomatia agglutinin (HPA) identifies oligosaccharides associated with poor-prognosis cancer. Our aim was to identify oligosaccharides that bind HPA in aggressive breast cancers. Breast-cancer cell lines (MCF-7, BT-549 and BT-20) and a cell line from human milk (HBL-100), which showed a range of HPA-binding intensities, were used to extract HPA-binding glycoproteins. Oligosaccharides were released using anhydrous hydrazine and separated on a range of HPLC matrices. We investigated whether HPA-binding oligosaccharides from cell lines were present in human breast-cancer tissues, using 69 breast-cancer specimens from patients with between 5 and 10 years' follow-up. A monosialylated oligosaccharide was over-expressed in the cell line that bound HPA strongly. Further analysis by normal-phase HPLC showed that the 2-aminobenzamide-conjugated oligosaccharide had a hydrodynamic volume of 4.58 glucose units (HPAgly1). Increased expression of HPAgly1 was associated with HPA staining of breast-cancer specimens (Student's t-test p = 0.025). Analysis of oligosaccharide levels and disease-free survival after treatment for breast cancer indicated a shorter disease-free interval for patients with elevated levels of HPAgly1. This is the first time that histochemical lectin staining has been correlated with biochemical mapping of oligosaccharides. Using this approach, we have identified a monosialylated HPA lectin-binding oligosaccharide present in breast-cancer cells grown in vitro which is elevated in breast-cancer specimens that bind the lectin.
KW - Adult
KW - Breast Neoplasms
KW - Carcinoma, Ductal, Breast
KW - Cell Line
KW - Chromatography, Affinity
KW - Chromatography, High Pressure Liquid
KW - Chromatography, Ion Exchange
KW - Disease-Free Survival
KW - Female
KW - Fluorescent Dyes
KW - Humans
KW - Lectins
KW - Middle Aged
KW - Oligosaccharides
KW - Prognosis
KW - Protein Binding
KW - Retrospective Studies
KW - Time Factors
KW - Treatment Outcome
KW - Tumor Cells, Cultured
KW - ortho-Aminobenzoates
M3 - SCORING: Journal article
C2 - 11241316
VL - 95
SP - 79
EP - 85
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 2
ER -