Internalization and Trafficking of CSPG-Bound Recombinant VAR2CSA Lectins in Cancer Cells Article Swipe
Chris Kedong Wang
,
Irina Nelepcu
,
Desmond Hui
,
Htoo Zarni Oo
,
Sarah Truong
,
Sarah Zhao
,
Shaghayegh Esfandnia
,
Fariba Ghaidi
,
Hans Adomat
,
Robert Dagil
,
Tobias Gustavsson
,
Swati Choudhary
,
Ali Salanti
,
Poul Sørensen
,
Nader Al-Nakouzi
,
Mads Daugaard
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-705229/v1
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-705229/v1
Proteoglycans are proteins that are modified with glycosaminoglycan chains. Chondroitin sulfate proteoglycans (CSPGs) are currently being exploited as targets for drug-delivery in various cancer indications, however basic knowledge on how CSPGs are internalized in tumor cells is lacking. In this study we took advantage of a recombinant CSPG-binding lectin VAR2CSA (rVAR2) to track internalization and cell fate of CSPGs in tumor cells. We found that rVAR2 is internalized into cancer cells via multiple internalization mechanisms after initial docking on cell surface CSPGs. Regardless of the internalization pathway used, CSPG-bound rVAR2 was trafficked to the early endosomes in an energy-dependent manner but not further transported to the lysosomal compartment. Instead, internalized CSPG-bound rVAR2 proteins were secreted with exosomes to the extracellular environment in a strictly chondroitin sulfate-dependent manner. In summary, our work describes the cell fate of rVAR2 proteins in tumor cells after initial binding to CSPGs, which can be further used to inform development of rVAR2-drug conjugates and other therapeutics targeting CSPGs.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-705229/v1
- https://www.researchsquare.com/article/rs-705229/latest.pdf
- OA Status
- green
- References
- 49
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3184699562
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3184699562Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.21203/rs.3.rs-705229/v1Digital Object Identifier
- Title
-
Internalization and Trafficking of CSPG-Bound Recombinant VAR2CSA Lectins in Cancer CellsWork title
- Type
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preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2021Year of publication
- Publication date
-
2021-07-16Full publication date if available
- Authors
-
Chris Kedong Wang, Irina Nelepcu, Desmond Hui, Htoo Zarni Oo, Sarah Truong, Sarah Zhao, Shaghayegh Esfandnia, Fariba Ghaidi, Hans Adomat, Robert Dagil, Tobias Gustavsson, Swati Choudhary, Ali Salanti, Poul Sørensen, Nader Al-Nakouzi, Mads DaugaardList of authors in order
- Landing page
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https://doi.org/10.21203/rs.3.rs-705229/v1Publisher landing page
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https://www.researchsquare.com/article/rs-705229/latest.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.researchsquare.com/article/rs-705229/latest.pdfDirect OA link when available
- Concepts
-
Internalization, Endosome, Chondroitin sulfate, Cell biology, Cancer cell, Microvesicles, Chemistry, Cell, Biology, Glycosaminoglycan, Biochemistry, Cancer, microRNA, Gene, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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49Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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