Galectin-1-binding glycoforms of haptoglobin with altered intracellular trafficking, and increase in metastatic breast cancer patients.

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Galectin-1-binding glycoforms of haptoglobin with altered intracellular trafficking, and increase in metastatic breast cancer patients.

Carlsson, Michael (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Cederfur, Cecilia (author): Lund University,Lunds universitet,Neuronano Research Center (NRC),Forskargrupper vid Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Lund University Research Groups,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Schaar, Viveka (author): Lund University,Lunds universitet,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Microbiology, Malmö,Lund University Research Groups

Balog, Crina I A (author)

Lepur, Adriana (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Touret, Franck (author)

Salomonsson, Emma (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Deelder, André M (author)

Fernö, Mårten (author): Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine

Olsson, Håkan (author): Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine

Wuhrer, Manfred (author)

Leffler, Hakon (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

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2011-10-18
2011
English.
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:10

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Journal article (peer-reviewed)

Abstract Subject headings

Sera from 25 metastatic breast cancer patients and 25 healthy controls were subjected to affinity chromatography using immobilized galectin-1. Serum from the healthy subjects contained on average 1.2 mg per ml (range 0.7-2.2) galectin-1 binding glycoproteins, whereas serum from the breast cancer patients contained on average 2.2 mg/ml (range 0.8-3.9), with a higher average for large primary tumours. The major bound glycoproteins were α-2-macroglobulin, IgM and haptoglobin. Both the IgM and haptoglobin concentrations were similar in cancer compared to control sera, but the percentage bound to galectin-1 was lower for IgM and higher for haptoglobin: about 50% (range 20-80) in cancer sera and about 30% (range 25-50) in healthy sera. Galectin-1 binding and non-binding fractions were separated by affinity chromatography from pooled haptoglobin from healthy sera. The N-glycans of each fraction were analyzed by mass spectrometry, and the structural differences and galectin-1 mutants were used to identify possible galectin-1 binding sites. Galectin-1 binding and non-binding fractions were also analyzed regarding their haptoglobin function. Both were similar in forming complex with haemoglobin and mediate its uptake into alternatively activated macrophages. However, after uptake there was a dramatic difference in intracellular targeting, with the galectin-1 non-binding fraction going to a LAMP-2 positive compartment (lysosomes), while the galectin-1 binding fraction went to larger galectin-1 positive granules. In conclusion, galectin-1 detects a new type of functional biomarker for cancer: a specific type of glycoform of haptoglobin, and possibly other serum glycoproteins, with a different function after uptake into tissue cells.

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By the author/editor: Carlsson, Michae ...; Cederfur, Cecili ...; Schaar, Viveka; Balog, Crina I A; Lepur, Adriana; Touret, Franck; show more...; Salomonsson, Emm ...; Deelder, André M; Fernö, Mårten; Olsson, Håkan; Wuhrer, Manfred; Leffler, Hakon; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Microbiology in ...

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Galectin-1-binding glycoforms of haptoglobin with altered intracellular trafficking, and increase in metastatic breast cancer patients.

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