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Glucose transporter-1 expression and the antiproliferative effects of 2-deoxy-d-glucose in osteosarcoma models

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dc.contributor.authorLori, Janet Carolyn, author
dc.contributor.authorLana, Susan E., advisor
dc.contributor.authorThamm, Douglas, advisor
dc.contributor.authorBiller, Barbara J., committee member
dc.contributor.authorEhrhart, Eugene J., committee member
dc.date.accessioned2022-07-01T00:08:26Z
dc.date.available2022-07-01T00:08:26Z
dc.date.issued2010
dc.description.abstractOsteosarcoma (OSA) is the most common bone tumor in the dog, more common in large to giant breed dogs. 90% of dogs diagnosed with OSA will die of metastatic disease within one year of diagnosis. There have been no great advances in therapy for canine OSA over the last 20 years. Hypoxia in tumors has been associated with an increased resistance to radiation and chemotherapy, and increased metastatic potential. Hypoxia-inducible factor 1-a (HIF-la) is a transcription factor stabilized by hypoxia. Glucose transporter 1 (GLUT-1), a downstream product of HIF-la pathway activation, is over-expressed in a variety of human tumors. We sought to determine if GLUT-1 is expressed in canine OSA and if expression is related to tumor necrosis and outcome. Immunohistochemistry was performed on 44 histologically confirmed OSA tissue samples to assess expression of GLUT-1. Of 44 cases, 27 (61%) expressed GLUT-1. There was no statistical correlation between GLUT-1 and disease-free interval, survival time, or percent necrosis. As hypothesized, GLUT-1 is present in most canine appendicular OSA. A more objective evaluation of GLUT-1 and other proteins in the HIF-la pathway may be warranted. Some cells within a tumor may be poorly perfused, and therefore less susceptible to traditional chemotherapy. Cancer cells, especially those hypoxic cells that are distant from the stromal blood vessels, require more glucose than normal cells as they utilize anaerobic glycolysis, rather than oxidative phosphorylation, to survive. 2-deoxy-Dglucose (2-DG) is a glucose analog that is preferentially captured by cancer cells, _ blocking the first step of glycolysis. We evaluated the sensitivity of various OSA (canine and murine) cell lines to 2-DG, and attempted correlation to the protein GLUT-1 with western analysis. There was no statistical correlation between 2-DG and GLUT-1 or Akt expression, although it did correlate with total ERK expression. In a murine OSA model, 2-DG was shown to inhibit metastasis, possibly through the inhibition of invasion and migration, as assessed by Boyden chamber assays in vitro using the same OSA murine cell line.
dc.format.mediummasters theses
dc.identifier.urihttps://hdl.handle.net/10217/235404
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relationCatalog record number (MMS ID): 991014531519703361
dc.relationSF992.C35 L67 2010
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subject.lcshDogs -- Diseases
dc.subject.lcshOsteosarcoma
dc.subject.lcshCancer in animals
dc.titleGlucose transporter-1 expression and the antiproliferative effects of 2-deoxy-d-glucose in osteosarcoma models
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineClinical Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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