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Galectin binding proteins in serum and bronchoalveolar lavage -in healthy and pathological conditions

Cederfur, Cecilia LU (2008) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2008:68.
Abstract
Galectins are carbohydrate binding proteins, implicated in conditions of both inflammation and cancer. Connections between chronic inflammation and cancer are proposed by the increased remodelling and proliferation that occurs, leading to enhanced survival and proliferation of malignant cells. Since galectins have been implicated in mechanisms of both chronic inflammation and cancer, we have investigated natural binding partners of galectins in healthy individuals and then continued with studying states of cancer and chronic inflammation. We identified galectin binding glycoproteins in sera from healthy individuals and found that galectins widely expressed in the body bind serum glycoproteins well, whereas galectins with a more... (More)
Galectins are carbohydrate binding proteins, implicated in conditions of both inflammation and cancer. Connections between chronic inflammation and cancer are proposed by the increased remodelling and proliferation that occurs, leading to enhanced survival and proliferation of malignant cells. Since galectins have been implicated in mechanisms of both chronic inflammation and cancer, we have investigated natural binding partners of galectins in healthy individuals and then continued with studying states of cancer and chronic inflammation. We identified galectin binding glycoproteins in sera from healthy individuals and found that galectins widely expressed in the body bind serum glycoproteins well, whereas galectins with a more tissue-specific distribution scarcely binds any serum glycoproteins. We then chose the widely expressed but intermediately binding galectin-1 to detect if levels of galectin-1-binding proteins are increased in sera of breast cancer patients. We found that galectin-1 binds approximately double the amount in breast cancer patients compared to healthy individuals. The increase was mainly caused by haptoglobin, probably due to both increased expression and changes of glycosylation.
To further investigate the inflammatory connection we identified galectin binding proteins from bronchoalveolar lavage of asthma patients and healthy individuals, additionally we compared the binding of galectin-3 and galectin-8 that are expressed in different sites of the lung. We found when functionally grouping the bound proteins that galectin-3 and -8 binding proteins had different profiles and that bound proteins of healthy and asthma patients differed. (Less)
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author
supervisor
oppenent
  • professor Peter Påhlsson, Linköpings Universitet
organization
year
type
Dissertation (Composite)
subject
keywords
cancer, glycoprotein, asthma, bronchoalveolar lavage, galectin binding protein, galectin ligand, galectin, serum
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2008:68
pages
73 pages
publisher
Dept of Laboratory Medicine, Lund University
defense location
Segerfalksalen, Wallenberg neurocentrum, BMC, Sölvegatan 17
defense date
2008-05-31 09:00
ISSN
1652-8220
ISBN
978-91-86059-21-7
language
English
LU publication?
yes
id
1148923
references
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MANUS I
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MANUS II
1. Rabinovich, G. A., Cumashi, A., Bianco, G. A., Ciavardelli, D., Iurisci, I., D'Egidio, M., Piccolo, E., Tinari, N., Nifantiev, N., and Iacobelli, S. Synthetic lactulose amines: novel class of anticancer agents that induce tumor-cell apoptosis and inhibit galectin-mediated homotypic cell aggregation and endothelial cell morphogenesis. Glycobiology, 16: 210-220, 2006.
2. Thijssen, V. L., Postel, R., Brandwijk, R. J., Dings, R. P., Nesmelova, I., Satijn, S., Verhofstad, N., Nakabeppu, Y., Baum, L. G., Bakkers, J., Mayo, K. H., Poirier, F., and Griffioen, A. W. Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci U S A, 103: 15975-15980, 2006.
3. Liu, F. T. and Rabinovich, G. A. Galectins as modulators of tumour progression. Nat Rev Cancer, 5: 29-41, 2005.
4. Rubinstein, N., Alvarez, M., Zwirner, N. W., Toscano, M. A., Ilarregui, J. M., Bravo, A., Mordoh, J., Fainboim, L., Podhajcer, O. L., and Rabinovich, G. A. Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; A potential mechanism of tumor-immune privilege. Cancer Cell, 5: 241-251, 2004.
5. Lau, K. S., Partridge, E. A., Grigorian, A., Silvescu, C. I., Reinhold, V. N., Demetriou, M., and Dennis, J. W. Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell, 129: 123-134, 2007.
6. Hakomori, S. and Handa, K. Glycosphingolipid-dependent cross-talk between glycosynapses interfacing tumor cells with their host cells: essential basis to define tumor malignancy. FEBS Lett, 531: 88-92, 2002.
7. Salatino, M., Croci, D. O., Bianco, G. A., Ilarregui, J. M., Toscano, M. A., and Rabinovich, G. A. Galectin-1 as a potential therapeutic target in autoimmune disorders and cancer. Expert Opin Biol Ther, 8: 45-57, 2008.
8. Thijssen, V. L., Poirier, F., Baum, L. G., and Griffioen, A. W. Galectins in the tumor endothelium; opportunities for combined cancer therapy. Blood, 2007.
9. Strik, H. M., Deininger, M. H., Frank, B., Schluesener, H. J., and Meyermann, R. Galectin-3: cellular distribution and correlation with WHO-grade in human gliomas. J Neurooncol, 53: 13-20, 2001.
10. Jung, E. J., Moon, H. G., Cho, B. I., Jeong, C. Y., Joo, Y. T., Lee, Y. J., Hong, S. C., Choi, S. K., Ha, W. S., Kim, J. W., Lee, C. W., Lee, J. S., and Park, S. T. Galectin-1 expression in cancer-associated stromal cells correlates tumor invasiveness and tumor progression in breast cancer. Int J Cancer, 120: 2331-2338, 2007.
11. Saussez, S., Lorfevre, F., Lequeux, T., Laurent, G., Chantrain, G., Vertongen, F., Toubeau, G., Decaestecker, C., and Kiss, R. The determination of the levels of circulating galectin-1 and -3 in HNSCC patients could be used to monitor tumor progression and/or responses to therapy. Oral Oncol, 2007.
12. Bresalier, R. S., Byrd, J. C., Tessler, D., Lebel, J., Koomen, J., Hawke, D., Half, E., Liu, K. F., and Mazurek, N. A circulating ligand for galectin-3 is a haptoglobin-related glycoprotein elevated in individuals with colon cancer. Gastroenterology, 127: 741-748, 2004.
13. Cederfur, C., Salomonsson, E., Nilsson, J., Halim, A., Oberg, C. T., Larson, G., Nilsson, U. J., and Leffler, H. Different affinity of galectins for human serum glycoproteins: galectin-3 binds many protease inhibitors and acute phase proteins. Glycobiology, 2008.
14. Hirabayashi, J., Hashidate, T., Arata, Y., Nishi, N., Nakamura, T., Hirashima, M., Urashima, T., Oka, T., Futai, M., Muller, W. E., Yagi, F., and Kasai, K. Oligosaccharide specificity of galectins: a search by frontal affinity chromatography. Biochim Biophys Acta, 1572: 232-254., 2002.
15. Anderson, N. L. and Anderson, N. G. The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics, 1: 845-867, 2002.
16. Huang, H. L., Stasyk, T., Morandell, S., Dieplinger, H., Falkensammer, G., Griesmacher, A., Mogg, M., Schreiber, M., Feuerstein, I., Huck, C. W., Stecher, G., Bonn, G. K., and Huber, L. A. Biomarker discovery in breast cancer serum using 2-D differential gel electrophoresis/ MALDI-TOF/TOF and data validation by routine clinical assays. Electrophoresis, 27: 1641-1650, 2006.
17. Saldova, R., Royle, L., Radcliffe, C. M., Hamid, U. M., Evans, R., Arnold, J. N., Banks, R. E., Hutson, R., Harvey, D. J., Antrobus, R., Petrescu, S. M., Dwek, R. A., and Rudd, P. M. Ovarian Cancer is Associated With Changes in Glycosylation in Both Acute-Phase Proteins and IgG. Glycobiology, 2007.
18. Toscano, M. A., Bianco, G. A., Ilarregui, J. M., Croci, D. O., Correale, J., Hernandez, J. D., Zwirner, N. W., Poirier, F., Riley, E. M., Baum, L. G., and Rabinovich, G. A. Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nat Immunol, 8: 825-834, 2007.


MANUS III
1. Bjermer L. Time for a paradigm shift in asthma treatment: from relieving bronchospasm to controlling systemic inflammation. J Allergy Clin Immunol 2007;120:1269-75.
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4. Mauad T, Bel EH, Sterk PJ. Asthma therapy and airway remodeling. J Allergy Clin Immunol 2007;120:997-1009; quiz 10-1.
5. Plymoth A, Yang Z, Lofdahl CG, Ekberg-Jansson A, Dahlback M, Fehniger TE, et al. Rapid proteome analysis of bronchoalveolar lavage samples of lifelong smokers and never-smokers by micro-scale liquid chromatography and mass spectrometry. Clin Chem 2006;52:671-9.
6. Magi B, Bargagli E, Bini L, Rottoli P. Proteome analysis of bronchoalveolar lavage in lung diseases. Proteomics 2006;6:6354-69.
7. Rudd PM, Elliott T, Cresswell P, Wilson IA, Dwek RA. Glycosylation and the immune system. Science 2001;291:2370-6.
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9. Cederfur C, Salomonsson E, Nilsson J, Halim A, Oberg CT, Larson G, et al. Different affinity of galectins for human serum glycoproteins: galectin-3 binds many protease inhibitors and acute phase proteins. Glycobiology 2008.
10. Lahm H, Andre S, Hoeflich A, Kaltner H, Siebert HC, Sordat B, et al. Tumor galectinology: insights into the complex network of a family of endogenous lectins. Glycoconj J 2004;20:227-38.
11. Nishi N, Shoji H, Seki M, Itoh A, Miyanaka H, Yuube K, et al. Galectin-8 modulates neutrophil function via interaction with integrin alphaM. Glycobiology 2003;13:755-63.
12. Huflejt ME, Leffler H. Galectin-4 in normal tissues and cancer. Glycoconj J 2004;20:247-55.
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date added to LUP
2008-05-09 11:22:34
date last changed
2009-01-19 14:31:56
@phdthesis{1148923,
  abstract     = {Galectins are carbohydrate binding proteins, implicated in conditions of both inflammation and cancer. Connections between chronic inflammation and cancer are proposed by the increased remodelling and proliferation that occurs, leading to enhanced survival and proliferation of malignant cells. Since galectins have been implicated in mechanisms of both chronic inflammation and cancer, we have investigated natural binding partners of galectins in healthy individuals and then continued with studying states of cancer and chronic inflammation. We identified galectin binding glycoproteins in sera from healthy individuals and found that galectins widely expressed in the body bind serum glycoproteins well, whereas galectins with a more tissue-specific distribution scarcely binds any serum glycoproteins. We then chose the widely expressed but intermediately binding galectin-1 to detect if levels of galectin-1-binding proteins are increased in sera of breast cancer patients. We found that galectin-1 binds approximately double the amount in breast cancer patients compared to healthy individuals. The increase was mainly caused by haptoglobin, probably due to both increased expression and changes of glycosylation. 
To further investigate the inflammatory connection we identified galectin binding proteins from bronchoalveolar lavage of asthma patients and healthy individuals, additionally we compared the binding of galectin-3 and galectin-8 that are expressed in different sites of the lung. We found when functionally grouping the bound proteins that galectin-3 and -8 binding proteins had different profiles and that bound proteins of healthy and asthma patients differed.},
  author       = {Cederfur, Cecilia},
  isbn         = {978-91-86059-21-7},
  issn         = {1652-8220},
  keyword      = {cancer,glycoprotein,asthma,bronchoalveolar lavage,galectin binding protein,galectin ligand,galectin,serum},
  language     = {eng},
  pages        = {73},
  publisher    = {Dept of Laboratory Medicine, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Galectin binding proteins in serum and bronchoalveolar lavage -in healthy and pathological conditions},
  volume       = {2008:68},
  year         = {2008},
}