Cell walls of seagrasses from the Baltic, the Mediterranean, the Red sea and the Indian Ocean– a new source of galactans for interaction with human galectins
Final Report Abstract
In the first part of the project, basic research on cell wall composition of eight seagrass species from the Baltic Sea, the Mediterranean Sea, the Red Sea and the Indian Ocean was performed. This is of evolutionary (adapation to the marine environment) and technological (seagrasses as source of environmentally friendly material) interest. In all species unusual pectins, the so-called apiogalacturonans (AGAs) were identified as typical components of the different seagrass families. The both Australian species Amphibolis antarctica and Posidonia australis contain lignins especially in roots and rhizomes, whereas E. acoroides and Zostera marina are nearly lignin-free. With analytical and bioinformatic methods, we were able to isolate and characterize arabinogalactan-proteins (AGPs) from eight seagrass species. All seagrass AGPs were rich in terminal glucuronic acid residues; obviously a convergent adaptation to the marine habitat. Alltogether, our work gives a comprehensive overview on cell walls of the different seagrass families. The adaptation to life in salt water needed basic new cell wall features, namely AGAs and uronic-acid-rich AGPs. Both molecules are able to bind Ca2+. This offers direct protection against penetration of sodium ions into the cell and can additionally trigger signal cascades in case of stress. In the second part of the project, seagrass-AGPs and further galactans of plant or synthetic origin were used to evaluate their potential as inhibitors of human galectins. Galectins are galactose-binding receptors, which play a role in tumor progression and metastasis, especially in case of galectin-1, -3, -7 and -9, and are therefore interesting new targets in tumor therapy. At first, different partial hydrolyses were used to produce galactans of changed structure and lower molecular weight. Next, binding capacities of these galactans to the different galectins were quantified by biolayer-interferometry. For the galactan from Echinacea purpurea, interaction with galectin-1 and -7 was proven. All tested galactans (from larch, from Echinacea, from Zostera marina as well as synthetic molecules with terminal galactose or lactose) revealed binding affinities to galectin-3 in the lower micromolar range, whereas only the seagrass-galactan interacted with galectin-9. Our investigations show the potential of galactans as galectin-antagonists and reveal specificities of some galactans for single galectins. Investigations of two different pancreatic cancer cell lines (Panc1 and Panc89) revealed that galectin-3 was expressed by both cell lines with a significantly higher galectin-3 level in Panc1 cells compared to Panc89 cells. Conversely, galectin-9 was only detected in Panc89 cells. Treatment of either cell line and the derived cell variants with the different galactans did only marginally impact cell growth and cell migration.
Publications
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Degraded Arabinogalactans and Their Binding Properties to Cancer-Associated Human Galectins. International Journal of Molecular Sciences, 22(8), 4058.
Pfeifer, Lukas; Baumann, Alexander; Petersen, Lea Madlen; Höger, Bastian; Beitz, Eric & Classen, Birgit
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Profiling the cell walls of seagrasses from A (Amphibolis) to Z (Zostera). BMC Plant Biology, 22(1).
Pfeifer, Lukas; van Erven, Gijs; Sinclair, Elizabeth A.; Duarte, Carlos M.; Kabel, Mirjam A. & Classen, Birgit
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Seagrass arabinogalactan-proteins: Are they important for adaptation to the marine environment?. openRxiv.
Pfeifer, Lukas; Johnson, Kim L.; Bacic, Antony; Reusch, Thorsten B. H.; Duarte, Carlos M.; Sinclair, Elizabeth A. & Classen, Birgit
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Synthetic and plant-derived multivalent galactans as modulators of cancer-associated galectins-3 and -9. openRxiv.
Pfeifer, Lukas; Mueller, Kim-Kristine; Müller, Maximilian Thal; Philipp, Lisa-Marie; Sebens, Susanne & Classen, Birgit
