Cancer processes probed by multivalency: investigations with galectin-3 and lactose functionalized dendrimers

dc.contributor.advisorChairperson, Graduate Committee: Mary J. Cloningeren
dc.contributor.authorFricke, Mackenzie Sueen
dc.contributor.otherSamuel P. Bernhard was an author and Willy Totten, Katarina Achazi, Paul Hillman, Rainer Haag and Mary J. Cloninger were co-authors of the article, 'The toxicity, uptake, and impact on galectin-3 mediated apoptosis of lactose functionalized dendrimers' submitted to the journal 'Biomolecules special issue: moving forward with dendrimers' which is contained within this thesis.en
dc.contributor.otherKyle Tweedy and Mary J. Cloninger were co-authors of the article, 'Lactose functionalized dendrimers impact galectin-3 mediated cancer cell migration in vitro' submitted to the journal 'ACS chemical biology' which is contained within this thesis.en
dc.date.accessioned2021-05-19T15:52:56Z
dc.date.available2021-05-19T15:52:56Z
dc.date.issued2019en
dc.description.abstractCancer has become a prevalent disease that is the second leading cause of death in the United States. Various cancers have been identified as either over or under expressing a sugar binding protein: galectin-3. The target of this research is to investigate cancerous events that are impacted by galectin-3 and mediate these events through the use of a multivalent binding partner to galectin-3. This binding partner is lactose functionalized PAMAM dendrimers. Apoptosis has been reported as another phenomenon that galectin-3 impacts. By using a reporter assay, viability, cytotoxicity and apoptosis were observed for cancer cell line A549 in the presence of exogenously added galectin-3 and/or lactose functionalized dendrimers. It was found that exogenous galectin-3 and glycodendrimers did not have any significant impact on these cell viability tests. Therefore, glycodendrimers can be used to probe multivalent effects without threat of toxicity. Metastasis was investigated through a modified in vitro scratch assay. By monitoring the migration of cancer cells, it was found that exogenously added galectin-3 retarded cell migration. When glycodendrimers were included, migration was partially restored. This revealed the implications of exogenous galectin-3 regarding the metastatic potential of carcinomas. When the implications of the domains of galectin-3 were investigated, it was found that the truncated galectin-3 containing only the carbohydrate recognition domain (CRD) was unable to replicate the same effects observed in full length galectin-3. Immunofluorescence microscopy was used to locate the multivalent binding partner and galectin-3 in the assay. While endocytosis of galectin-3 was observed, no colocalization with the multivalent binding partner was observed intracellularly, supporting the hypothesis of an extracellular interaction mediating the results. Multivalent interactions between glycodendrimers and galectin-3 impacted cellular migration. Angiogenesis revealed that exogenous galectin-3 induced neovascularization. Glycodendrimers impacted galectin-3 mediated angiogenesis. Glycodendrimers alone could elicit effects either enhancing or negating angiogenesis depending on the dendrimer generation. Fluorescent tags revealed glycodendrimer accumulation on or inside the cells and galectin-3 on the surface of cell groups. Overall, these studies show that glycodendrimers can interact multivalently and affect cellular processes.en
dc.identifier.urihttps://scholarworks.montana.edu/handle/1/16185en
dc.language.isoenen
dc.publisherMontana State University - Bozeman, College of Letters & Scienceen
dc.rights.holderCopyright 2019 by Mackenzie Sue Frickeen
dc.subject.lcshCanceren
dc.subject.lcshLectinsen
dc.subject.lcshDendrimersen
dc.subject.lcshMetastasisen
dc.subject.lcshCell deathen
dc.titleCancer processes probed by multivalency: investigations with galectin-3 and lactose functionalized dendrimersen
dc.typeDissertationen
mus.data.thumbpage168en
thesis.degree.committeemembersMembers, Graduate Committee: C. Martin Lawrence; Valerie Copie; Joan B. Brodericken
thesis.degree.departmentChemistry & Biochemistry.en
thesis.degree.genreDissertationen
thesis.degree.namePhDen
thesis.format.extentfirstpage1en
thesis.format.extentlastpage180en

Files

Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
fricke-cancer-processes-2019.pdf
Size:
8.42 MB
Format:
Adobe Portable Document Format
Description:
Cancer processes probed by multivalency (PDF)
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
826 B
Format:
Plain Text
Description:
Copyright (c) 2002-2022, LYRASIS. All rights reserved.