Internalization and trafficking of CSPG-bound recombinant VAR2CSA lectins in cancer cells
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Internalization and trafficking of CSPG-bound recombinant VAR2CSA lectins in cancer cells. / Wang, Chris Kedong; Nelepcu, Irina; Hui, Desmond; Oo, Htoo Zarni; Truong, Sarah; Zhao, Sarah; Tahiry, Zakir; Esfandnia, Shaghayegh; Ghaidi, Fariba; Adomat, Hans; Dagil, Robert; Gustavsson, Tobias; Choudhary, Swati; Salanti, Ali; Sorensen, Poul H; Al Nakouzi, Nader; Daugaard, Mads.
In: Scientific Reports, Vol. 12, 3075, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Internalization and trafficking of CSPG-bound recombinant VAR2CSA lectins in cancer cells
AU - Wang, Chris Kedong
AU - Nelepcu, Irina
AU - Hui, Desmond
AU - Oo, Htoo Zarni
AU - Truong, Sarah
AU - Zhao, Sarah
AU - Tahiry, Zakir
AU - Esfandnia, Shaghayegh
AU - Ghaidi, Fariba
AU - Adomat, Hans
AU - Dagil, Robert
AU - Gustavsson, Tobias
AU - Choudhary, Swati
AU - Salanti, Ali
AU - Sorensen, Poul H
AU - Al Nakouzi, Nader
AU - Daugaard, Mads
N1 - © 2022. The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-022-07025-6
DO - 10.1038/s41598-022-07025-6
M3 - Journal article
C2 - 35197518
VL - 12
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 3075
ER -
ID: 298630292