Oligosaccharide Sequence of Human Breast Cancer Cell Heparan Sulfate with High Affinity for Laminin

Parthasarathy, Narayanan; Gotow, Lisa F.; Bottoms, J D; Kute, Timothy E.; Wagner, William D.; Mulloy, Barbara

doi:10.1074/jbc.273.33.21111

Cited by 18 publications

(9 citation statements)

References 38 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, such synthetic methods are complex and have not been widely applied to the study of other biological sequences. An alternative approach involving affinity fractionation of HLGAGs with proteins of interest and subsequent characterization has provided some overall information regarding sulfation patterns that determine affinity (8)(9)(10). However, until recently there have been no effective methods to sequence these saccharides.…”

mentioning

confidence: 99%

Sequencing of 3-O sulfate containing heparin decasaccharides with a partial antithrombin III binding site

Shriver

Raman

Venkataraman

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

coagulation cascade. In this manner, HLGAGs play an important biological and pharmacological role in the modulation of blood clotting. Recently, a sequencing methodology was developed to further structure-function relationships of this important class of molecules. This methodology combines a property-encoded nomenclature scheme to handle the large information content (properties) of HLGAGs, with matrix-assisted laser desorption ionization MS and enzymatic and chemical degradation as experimental constraints to rapidly sequence picomole quantities of HLGAG oligosaccharides. Using the above property-encoded nomenclature-matrix-assisted laser desorption ionization approach, we found that the sequence of the decasaccharide used in this study is ⌬U 2SHNS,6SI2SHNS,6SI2SHNS,6S-IHNAc,6SGHNS,3S,6S (؎DDD4 -7). We confirmed our results by using integral glycan sequencing and one-dimensional proton NMR. Furthermore, we show that this approach is flexible and is able to derive sequence information on an oligosaccharide mixture. Thus, this methodology will make possible both the analysis of other unusual sequences in HLGAGs with important biological activity as well as provide the basis for the structural analysis of these pharamacologically important group of heparin͞heparan sulfates. H eparin-and heparan sulfate-like glycosaminoglycans (HLGAGs), present both at the cell surface and in the extracellular matrix, are a group of complex polysaccharides that are variable in length, consisting of a disaccharide repeat unit composed of glucosamine and an uronic acid (either iduronic or glucuronic acid). The high degree of complexity for HLGAGs arises not only from their polydispersity and the possibility of two different uronic acid components, but also from differential modification at four positions of the disaccharide unit. Three positions, namely, C2 of the uronic acid and the C3, C6 positions of the glucosamine can be O-sulfated. In addition, C2 of the glucosamine can be N-acetylated or N-sulfated. Together, these modifications theoretically could lead to 32 possible disaccharide units, making HLGAGs potentially more information dense than either DNA (four bases) or proteins (20 aa). This enormity of possible structural variants allows HLGAGs to be involved in a large number of diverse biological processes, including angiogenesis (1), embryogenesis (2-4), and the formation of ␤-fibrils in Alzheimer's disease (5, 6).This structural diversity is one of the factors that has made it difficult to study sequence-function relationships for HLGAGs. Chemical synthesis of defined oligosaccharides has been used in studying the relative contribution to high-affinity antithrombin III (AT-III) binding of specific modifications in the pentasaccharide sequence (7). However, such synthetic methods are complex and have not been widely applied to the study of other biological sequences. An alternative approach involving affinity fractionation of HLGAGs with proteins of interest and subsequent characterization has provided some overall informat...

show abstract

mentioning

confidence: 99%

Sequencing of 3-O sulfate containing heparin decasaccharides with a partial antithrombin III binding site

Shriver

Raman

Venkataraman

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Decreased VLDL uptake by BC cells in the presence of an antibody directed against HS NS4F5 implicates this specific HSPG motif as the binding moiety. Notably, the HS NS4F5 sequence (GlcNS6S-IdoA2S)3 is repeated in heparin and was previously identified as an LPL-binding sequence [33] found on the surface of MCF-7 BC cells [54]. Though MCF-7 and several other BC cell lines do not express detectable levels of LPL mRNA, they do display HS NS4F5 on their cell surface.…”

Section: Discussionmentioning

confidence: 99%

Endocytosis of very low-density lipoprotein particles: an unexpected mechanism for lipid acquisition by breast cancer cells

Lupien

Bloch

Dehairs

et al. 2019

Preprint

View full text Add to dashboard Cite

We previously described the expression of CD36 and lipoprotein lipase (LPL) by breast cancer (BC) cells and tissues, and the growth-promoting effect of very low-density lipoprotein (VLDL) supplementation observed in BC cell lines only in the presence of LPL. We now describe the deployment of LPL by BC cells. Our data support a model in which LPL is bound to a heparin-like heparan sulfate proteoglycan motif on the BC cell surface and acts in concert with the VLDL receptor to rapidly internalize intact lipoproteins via receptor-mediated endocytosis. We further observe substantial alterations in gene expression programs related to pathways for lipid acquisition (synthesis vs. uptake) in response to each the availability of exogenous triglyceride in tissue culture media and LPL expression status. Current literature emphasizes de novo fatty acid synthesis as the paramount mechanism for lipid acquisition by cancer cells. Our findings indicate that exogenous lipid uptake can serve as an important method of lipid acquisition for cancer cells, alongside de novo lipogenesis, and that the relative reliance on these two modes of lipid acquisition may vary among different BC cell lines and in response to nutrient availability. This concept has obvious implications for the development of therapies aimed at the lipid dependence of many different cancer types. Moreover, the mechanism that we have elucidated provides a direct connection between dietary fat and tumor biology. ________________________________________ The dependence of several tumor cell types, including breast cancer, on a supply of fatty acids to maintain proliferation is well established [1]. The literature emphasizes de novo lipid synthesis as the paramount mechanism used by tumor cells to satisfy this dependency. De novo lipogenesis is a cytosolic process that produces the saturated long-chain FA palmitate (C16:0), the bulk Endocytosis of VLDLs in BC

show abstract

“…We have not investigated this possibility in the described experiments. Early studies of heparan sulfate and dermatan sulfate show that these GAGs have high affinities for laminin, and that heparin modulates laminin polymerization in vitroin vitro (Parthasarathy et al, 1998;Yurchenco et al, 1990). Similarly, PGs interact with collagen in specific locations in order to maintain the structure and organization of the ECM (Gillies and Lieber, 2011).…”

Section: Discussionmentioning

confidence: 99%

The combination of glycosaminoglycans and fibrous proteins improves cell proliferation and early differentiation of bovine primary skeletal muscle cells

et al. 2013

View full text Add to dashboard Cite

Primary muscle cell model systems from farm animals are widely used to acquire knowledge about muscle development, muscle pathologies, overweight issues and tissue regeneration. The morphological properties of a bovine primary muscle cell model system, in addition to cell proliferation and differentiation features, were characterized using immunocytochemistry, western blotting and real-time PCR. We observed a reorganization of the Golgi complex in differentiated cells. The Golgi complex transformed to a highly fragmented network of small stacks of cisternae positioned throughout the myotubes as well as around the nucleus. Different extracellular matrix (ECM) components were used as surface coatings in order to improve cell culture conditions. Our experiments demonstrated improved proliferation and early differentiation for cells grown on surface coatings containing a mixture of both glycosaminoglycans (GAGs) and fibrous proteins. We suggest that GAGs and fibrous proteins mixed together into a composite biomaterial can mimic a natural ECM, and this could improve myogenesis for in vitroin vitro cell cultures.Abbreviations: used: ECMextracellular (The author would like to point out that there should be a space between the abbrevations and the subsequent explanation. ) matrix; GAGsglucosaminoglycans;MRFGAGsglucosaminoglycans, MRF, myogenic regulatory transcription factor; PGproteoglycan

show abstract

Oligosaccharide Sequence of Human Breast Cancer Cell Heparan Sulfate with High Affinity for Laminin

Cited by 18 publications

References 38 publications

Sequencing of 3-O sulfate containing heparin decasaccharides with a partial antithrombin III binding site

Sequencing of 3-O sulfate containing heparin decasaccharides with a partial antithrombin III binding site

Endocytosis of very low-density lipoprotein particles: an unexpected mechanism for lipid acquisition by breast cancer cells

The combination of glycosaminoglycans and fibrous proteins improves cell proliferation and early differentiation of bovine primary skeletal muscle cells

Contact Info

Product

Resources

About