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Title
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Effects of glycosylation on melanoma interactions with type IV collagen models.
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Creator
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Aukszi, Beatrix., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
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Abstract/Description
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Tumor cells interact with basement membrane collagen at the site of extravasation through distinct cellular receptors, including the α2β1 and α3β1integrins. These receptors are known to be differentially expressed in metastatic tumors, relative to the normal cells, depending on tumor type and stage of progression. The binding sites within type IV collagen for the α2β1 andα3β1 integrins have been identified. Since both of the integinspecific sequences possess at least one glycosylated Hyl...
Show moreTumor cells interact with basement membrane collagen at the site of extravasation through distinct cellular receptors, including the α2β1 and α3β1integrins. These receptors are known to be differentially expressed in metastatic tumors, relative to the normal cells, depending on tumor type and stage of progression. The binding sites within type IV collagen for the α2β1 andα3β1 integrins have been identified. Since both of the integinspecific sequences possess at least one glycosylated Hyl residue, we questioned whether glycosylation could modulate integrin binding. Triple-helical peptides with and without Lys substituted by glycosylated Hyl for Lys543 and Lys540 from the human a1(IV)531-543 gene sequence (α3β integrin-specific) and Lys393 from the human a1(IV)382-393 gene sequence (α2β1 integrin-specific) were synthesized and utilized in the present study., Cellular response to these triple helical ligands was tested with a primary melanoma cell line, WM-115, and three highly metastatic melanoma cell lines , WM-266-4, M14#5, and SK-MEL-2. Cell adhesion and cell spreading assays yielded differing results depending on whether the ligands contained glycosylated Hyl residues or not. In general, a decrease in cellular affinity toward the ligands was observed when glycosylated Hyl was present. Differences in the levels of adhesion and spreading between cell lines representing different stages of melanoma were also observed. Neutral B-galactosidase activity was detected in all four cell lines. Enzymatic activity levels were comparable for the three metastatic cell lines, whereas distinctively higher activity was detected for cells originating from a primary lesion. This acitivity can signal the potential of tumor cells to enhance and recover their invasive abilities., The ability of each cell line to remove the galactose from the peptide ligands has been investigated, to test whether tumor cells can reestablish binding relationships between the α2β1 and α3β1 integrins and type IV collagen that are reduced by glycosylation.
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Date Issued
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2008
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PURL
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http://purl.flvc.org/FAU/186335
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Subject Headings
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Animal cell biotechnology, Combinatorial chemistry, Integrins, Research, Methodology, Cell adhesion molecules, Physiological effect
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Format
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Document (PDF)
