Abstract
Bovine pancreatic ribonuclease (RNase A) can enter human cells, even though it lacks a cognate cell-surface receptor protein. Here, we report on the biochemical basis for its cellular uptake. Analyses in vitro and in cellulo revealed that RNase A interacts tightly with abundant cell-surface proteoglycans containing glycosaminoglycans, such as heparan sulfate and chondroitin sulfate, as well as with sialic acid-containing glycoproteins. The uptake of RNase A correlates with cell anionicity, as quantified by measuring electrophoretic mobility. The cellular binding and uptake of RNase A contrast with those of Onconase, an amphibian homologue that does not interact tightly with anionic cell-surface glycans. As anionic glycans are especially abundant on human tumor cells, our data predicate utility for mammalian ribonucleases as cancer chemotherapeutic agents.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Anions / chemistry*
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Anions / metabolism*
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CHO Cells
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Cattle
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Cell Line
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Cell Proliferation
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Chondroitin Sulfates / chemistry
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Chondroitin Sulfates / metabolism
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Chromatography, Affinity
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Cricetinae
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Cricetulus
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Flow Cytometry
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Glycoproteins / chemistry
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Glycoproteins / metabolism
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Glycosaminoglycans / chemistry
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Glycosaminoglycans / metabolism
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Heparitin Sulfate / chemistry
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Heparitin Sulfate / metabolism
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Humans
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Microscopy, Fluorescence
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Molecular Weight
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N-Acetylneuraminic Acid / chemistry
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Polysaccharides / chemistry*
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Polysaccharides / metabolism*
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Protein Binding
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Ribonuclease, Pancreatic / chemistry*
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Ribonuclease, Pancreatic / metabolism*
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Substances
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Anions
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Glycoproteins
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Glycosaminoglycans
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Polysaccharides
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Chondroitin Sulfates
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Heparitin Sulfate
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Ribonuclease, Pancreatic
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N-Acetylneuraminic Acid