Properties of a Human Metastatic Variant Lung Cancer Model

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dc.contributor.advisorMart Hart
dc.contributor.committeeMemberRobert Wordinger
dc.contributor.committeeMemberRick Kitson
dc.creatorPoirot, Julie E.
dc.date.accessioned2019-08-22T21:36:30Z
dc.date.available2019-08-22T21:36:30Z
dc.date.issued2003-05-01
dc.date.submitted2014-03-19T06:24:05-07:00
dc.description.abstractPoirot, J. Properties of a Human Metastatic Variant Lung Cancer Model. Master of Science (Molecular Biology and Immunology). May 2003. 44 pp., 11 illustrations, 1 table, 39 bibliography titles. A model of non-small cell lung cancer (NSCLC) has been developed for screening and preclinical drug evaluation by implanting the A549 lung cancer cell line orthotopically into immunocompromised (SCID) mice. Aggressive metastatic sublines were then derived from metastases from the primary implant. The purpose of this project is to elucidate some of the cellular properties involved in the tumor aggressiveness of the metastatic variant cell lines. In vitro migration and invasion assays produced data showing no significant differences between the rates of migration or invasion of parental and metastatic sublines. In vivo tumor burden experiments, however, produced data showing significant differences in the numbers and sizes of metastatic tumors formed when the three cell lines were compared in SCID mice. RT-PCR analysis has indicated that there are differences in the mRNA levels of certain matrix metalloproteinases. The A549 parental cells have matrix metalloproteinase-2 (MMP-2) but not MMP-9, while both metastatic variants show MMP-9 mRNA but no MMP-2. Western blots and gelatin zymographies also confirm these findings. RT-PCR analysis and casein zymography experiments have also shown no differences in the message or activity of urokinase plasminogen activator *uPA0 among the cell lines. Multidrug resistance studies were done on the tumor cell lines in order to compare their resistance to various classes of antineoplastic drugs. These studies indicate that there is no significant difference in the resistance to doxorubicin or paclitaxel, but the parental cell line is substantially more resistant to cisplatin than either of the metastatic sublines.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29456
dc.language.isoen
dc.provenance.legacyDownloads0
dc.subjectBiology
dc.subjectCancer Biology
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.subjectCells
dc.subjectCellular and Molecular Physiology
dc.subjectChemicals and Drugs
dc.subjectGenetics and Genomics
dc.subjectImmunology and Infectious Disease
dc.subjectLife Sciences
dc.subjectMedical Cell Biology
dc.subjectMedical Pharmacology
dc.subjectMedicine and Health Sciences
dc.subjectOncology
dc.subjectOther Cell and Developmental Biology
dc.subjectOther Genetics and Genomics
dc.subjectOther Pharmacy and Pharmaceutical Sciences
dc.subjectPharmacy and Pharmaceutical Sciences
dc.subjectHuman
dc.subjectmetastatic variant
dc.subjectlung cancer
dc.subjectmodel
dc.subjectdoxorubicin
dc.subjectpaclitaxel
dc.subjectresistance
dc.subjectnon-small cell lung cancer
dc.subjectNSCLC
dc.subjectdrug evaluation
dc.subjectimmunocompromised
dc.subjectmice
dc.subjectA549
dc.subjectaggressive metastatic sublines
dc.subjectin vivo burden experiments
dc.subjectRT-PCR analysis
dc.subjectmRNA
dc.subjectmetalloproteinases
dc.subjectcasein zymography
dc.subjecturokinase plasminogen activator
dc.titleProperties of a Human Metastatic Variant Lung Cancer Model
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentSchool of Public Health
thesis.degree.disciplineMicrobiology and Immunology
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameMaster of Science

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