Theses and Dissertations at Montana State University (MSU)
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Item Cancer processes probed by multivalency: investigations with galectin-3 and lactose functionalized dendrimers(Montana State University - Bozeman, College of Letters & Science, 2019) Fricke, Mackenzie Sue; Chairperson, Graduate Committee: Mary J. Cloninger; 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.; 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.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.Item The effects of baclofen on CaM Kinase following cerebral ischemia(Montana State University - Bozeman, College of Letters & Science, 1997) Everingham, Andrea Joe MaryItem Studies directed toward the synthesis of the C(19)-C(32) carbon fragment of Scytophycin C(Montana State University - Bozeman, College of Letters & Science, 2002) Swain, William RichardItem Expression profiling and function elucidation of anaplastic lymphoma kinase in the developing nervous system(Montana State University - Bozeman, College of Letters & Science, 2006) Hurley, Shawn Patrick; Chairperson, Graduate Committee: Frances LefcortDuring embryonic development, complex events such as cellular proliferation, differentiation, survival, and guidance of axons are orchestrated and regulated by a variety of extracellular signals. Receptor tyrosine kinases mediate many of these events with several playing critical roles in neuronal survival and axonal guidance. It is evident that not all the receptor tyrosine kinases that play key roles in regulating neuronal development have been identified. In these studies, we have characterized the spatial-temporal expression profile of a recently identified receptor tyrosine kinase, anaplastic lymphoma kinase (ALK), in embryonic chick by means of whole mount in situ hybridization in conjunction with immunohistochemistry. Our findings reveal that Alk is expressed in sympathetic and dorsal root ganglia as early as stage 19.