R Saldova1, J M Reuben2, U M Abd Hamid1, P M Rudd3, M Cristofanilli4. 1. NIBRT Dublin-Oxford Glycobiology Laboratory, The National Institute for Bioprocessing Research and Training, Conway Institute, University College Dublin, Belfield, Dublin, Ireland. 2. Departments of Hematopathology. 3. NIBRT Dublin-Oxford Glycobiology Laboratory, The National Institute for Bioprocessing Research and Training, Conway Institute, University College Dublin, Belfield, Dublin, Ireland. Electronic address: pauline.rudd@nibrt.ie. 4. Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
Abstract
BACKGROUND: Metastatic breast cancer (MBC) is currently an incurable condition that is primarily treated with palliative measures. Isolation of circulating tumor cells (CTCs) from the peripheral blood of these patients provides a predictive prognostic indicator, independent of the type of therapy, site of occurrence and biological characteristics of the primary disease. It has been well established that glycosylation processing pathways are disturbed in cancer, leading to alterations in the glycan content of glycoproteins. MATERIALS AND METHODS: The bi-, tri- and tetraantennary glycans containing sialyl Lewis x (sLe(x)) epitopes (A2F1G1, A3F1G1, A4F1G1 and A4F2G2) were quantified using normal phase high-performance liquid chromatography in combination with exoglycosidase array digestions in the glycan pools released from sera of 27 patients with advanced breast cancer (16 with CTCs <5/7.5 ml and 11 with CTCs ≥5/7.5 ml) and 13 healthy women. RESULTS: The levels of all these glycans were significantly higher in patients with CTCs ≥5/7.5 ml compared with patients with CTCs <5/7.5 ml. CONCLUSIONS: As high levels of glycans containing sLe(x) epitopes were associated with CTCs, their measurement may provide a new noninvasive approach for determining prognosis in women with MBC.
BACKGROUND:Metastatic breast cancer (MBC) is currently an incurable condition that is primarily treated with palliative measures. Isolation of circulating tumor cells (CTCs) from the peripheral blood of these patients provides a predictive prognostic indicator, independent of the type of therapy, site of occurrence and biological characteristics of the primary disease. It has been well established that glycosylation processing pathways are disturbed in cancer, leading to alterations in the glycan content of glycoproteins. MATERIALS AND METHODS: The bi-, tri- and tetraantennary glycans containing sialyl Lewis x (sLe(x)) epitopes (A2F1G1, A3F1G1, A4F1G1 and A4F2G2) were quantified using normal phase high-performance liquid chromatography in combination with exoglycosidase array digestions in the glycan pools released from sera of 27 patients with advanced breast cancer (16 with CTCs <5/7.5 ml and 11 with CTCs ≥5/7.5 ml) and 13 healthy women. RESULTS: The levels of all these glycans were significantly higher in patients with CTCs ≥5/7.5 ml compared with patients with CTCs <5/7.5 ml. CONCLUSIONS: As high levels of glycans containing sLe(x) epitopes were associated with CTCs, their measurement may provide a new noninvasive approach for determining prognosis in women with MBC.
Authors: Helene Bayer; Katharina Essig; Sven Stanzel; Martin Frank; Jeffrey C Gildersleeve; Martin R Berger; Cristina Voss Journal: J Biol Chem Date: 2012-08-07 Impact factor: 5.157