Glycocalyx Engineering with a Recycling Glycopolymer that Increases Cell Survival In Vivo

Woods, Elliot C.; Yee, Nathan A.; Shen, Jeff; Bertozzi, Carolyn R.

doi:10.1002/anie.201508783

Cited by 80 publications

(120 citation statements)

References 35 publications

Supporting

Mentioning

109

Contrasting

Unclassified

Order By: Relevance

“…Persistent and stable display of synthetic ligands is crucial for cell-surface engineering techniques to probe biological processes that occur on longer times scales. 10,15 …”

Section: Resultsmentioning

confidence: 99%

“…1–6 It provides a powerful means to elucidate molecular mechanisms by which specific biomolecules perform their functions and may find application in cell therapy by targeting therapeutic cells to specific tissues, 2,7–9 endowing cells with new functions such as recruiting/restoring protein binding or directing cell signaling or stem cell differentiation, 10–13 and altering immune cell responses toward cancerous cells. 14,15 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cell-Surface Glyco-Engineering by Exogenous Enzymatic Transfer Using a Bifunctional CMP-Neu5Ac Derivative

Capicciotti¹,

Zong²,

Sheikh³

et al. 2017

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Cell-surface engineering strategies that permit long-lived display of well-defined, functionally active molecules are highly attractive for eliciting desired cellular responses and for understanding biological processes. Current methodologies for the exogenous introduction of synthetic biomolecules often result in short-lived presentations, or require genetic manipulation to facilitate membrane attachment. Herein, we report a cell-surface engineering strategy that is based on the use of a CMP-Neu5Ac derivative that is modified at C-5 by a bifunctional entity composed of a complex synthetic heparan sulfate (HS) oligosaccharide and biotin. It is shown that recombinant ST6GAL1 can readily transfer the modified sialic acid to N-glycans of glycoprotein acceptors of living cells resulting in long-lived display. The HS oligosaccharide is functionally active, can restore protein binding, and allows activation of cell signaling events of HS-deficient cells. The cell-surface engineering methodology can easily be adapted to any cell type and is highly amenable to a wide range of complex biomolecules.

show abstract

“…Persistent and stable display of synthetic ligands is crucial for cell-surface engineering techniques to probe biological processes that occur on longer times scales. 10,15 …”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cell-Surface Glyco-Engineering by Exogenous Enzymatic Transfer Using a Bifunctional CMP-Neu5Ac Derivative

Capicciotti¹,

Zong²,

Sheikh³

et al. 2017

J. Am. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…We previously found that this particular lipid confers a long cell surface residence time to glycopolymer conjugates by mediating continuous recycling from an internal reservoir. (Woods et al, 2015) The core of the glycopolymer comprises N-acetylgalactosamine (GalNAc) residues affixed to a poly (methyl vinyl ketone [MVK]) backbone via oxime linkages. The spacing afforded by this structure approximates that of GalNAc-a-Ser/Thr clusters within native mucins.…”

Section: Introductionmentioning

confidence: 99%

A Bulky Glycocalyx Fosters Metastasis Formation by Promoting G1 Cell Cycle Progression

Woods

Barnes

Pickup

et al. 2017

Preprint

Self Cite

View full text Add to dashboard Cite

Metastasis depends upon cancer cell growth and survival within the metastatic niche.Tumors which remodel their glycocalyces, by overexpressing bulky glycoproteins like mucins, exhibit a higher predisposition to metastasize, but the role of mucins in oncogenesis remains poorly understood. Here we report that a bulky glycocalyx promotes the expansion of disseminated tumor cells in vivo by fostering integrin adhesion assembly to permit G1 cell cycle progression. We engineered tumor cells to display glycocalyces of various thicknesses by coating them with synthetic mucin-mimetic glycopolymers. Cells adorned with longer glycopolymers showed increased metastatic potential, enhanced cell cycle progression, and greater levels of integrin-FAK mechanosignaling and Akt signaling in a syngeneic mouse model of metastasis. These effects were mirrored by expression of the ectodomain of cancer-associated mucin MUC1. These findings functionally link mucinous proteins with tumor aggression, and offer a new view of the cancer glycocalyx as a major driver of disease progression.

show abstract

“…Additionally, some lipid-conjugated agents undergo rapid endocytosis (Capicciotti et al, 2017; Rabuka et al, 2008). Once internalized, the species may be degraded, become trapped within endosomes, or incorporated into intracellular membranes, making them inaccessible for mediating cell-cell interactions (Dutta et al, 2011a; Woods et al, 2015). …”

Section: Perspectivementioning

confidence: 99%

Programming Cell-Cell Interactions through Non-genetic Membrane Engineering

Csizmar

Petersburg

Wagner

2018

Cell Chemical Biology

View full text Add to dashboard Cite

The ability to direct targeted intercellular interactions has the potential to enable and expand the use of cell-based therapies for regenerative medicine, tissue engineering, and immunotherapy. While genetic engineering approaches have proven effective, these techniques are not amenable to all cell types and often yield permanent modifications with potentially long-lasting adverse effects, restricting their application. To circumvent these limitations, there is intense interest in developing non-genetic methods to modify cell membranes with functional groups that will enable the recognition of target cells. While many such techniques have been developed, relatively few have been applied to directing specific cell-cell interactions. This review details these non-genetic membrane engineering approaches-namely, hydrophobic membrane insertion, chemical modification, liposome fusion, metabolic engineering, and enzymatic remodeling-and summarizes their major applications. Based on this analysis, perspective is provided on the ideal features of these systems with an emphasis on the potential for clinical translation.

show abstract

Glycocalyx Engineering with a Recycling Glycopolymer that Increases Cell Survival In Vivo

Cited by 80 publications

References 35 publications

Cell-Surface Glyco-Engineering by Exogenous Enzymatic Transfer Using a Bifunctional CMP-Neu5Ac Derivative

Cell-Surface Glyco-Engineering by Exogenous Enzymatic Transfer Using a Bifunctional CMP-Neu5Ac Derivative

A Bulky Glycocalyx Fosters Metastasis Formation by Promoting G1 Cell Cycle Progression

Programming Cell-Cell Interactions through Non-genetic Membrane Engineering

Contact Info

Product

Resources

About