Cancer processes probed by multivalency: investigations with galectin-3 and lactose functionalized dendrimers
dc.contributor.advisor | Chairperson, Graduate Committee: Mary J. Cloninger | en |
dc.contributor.author | Fricke, Mackenzie Sue | en |
dc.contributor.other | Samuel 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.other | Kyle 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.accessioned | 2021-05-19T15:52:56Z | |
dc.date.available | 2021-05-19T15:52:56Z | |
dc.date.issued | 2019 | en |
dc.description.abstract | Cancer 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.uri | https://scholarworks.montana.edu/handle/1/16185 | en |
dc.language.iso | en | en |
dc.publisher | Montana State University - Bozeman, College of Letters & Science | en |
dc.rights.holder | Copyright 2019 by Mackenzie Sue Fricke | en |
dc.subject.lcsh | Cancer | en |
dc.subject.lcsh | Lectins | en |
dc.subject.lcsh | Dendrimers | en |
dc.subject.lcsh | Metastasis | en |
dc.subject.lcsh | Cell death | en |
dc.title | Cancer processes probed by multivalency: investigations with galectin-3 and lactose functionalized dendrimers | en |
dc.type | Dissertation | en |
mus.data.thumbpage | 168 | en |
thesis.degree.committeemembers | Members, Graduate Committee: C. Martin Lawrence; Valerie Copie; Joan B. Broderick | en |
thesis.degree.department | Chemistry & Biochemistry. | en |
thesis.degree.genre | Dissertation | en |
thesis.degree.name | PhD | en |
thesis.format.extentfirstpage | 1 | en |
thesis.format.extentlastpage | 180 | en |