Cell-surface Tumoricidal Molecules and NF-kB in the Tumor-burdened Host

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dc.contributor.authorMcConnell, Michael Jamesen
dc.contributor.committeechairElgert, Klaus D.en
dc.contributor.committeememberRutherford, Charles L.en
dc.contributor.committeememberWinkel, Brenda S. J.en
dc.contributor.departmentBiologyen
dc.date.accessioned2011-08-06T14:41:43Zen
dc.date.adate2003-10-30en
dc.date.available2011-08-06T14:41:43Zen
dc.date.issued2002-06-24en
dc.date.rdate2004-10-30en
dc.date.sdate2002-07-02en
dc.description.abstractTumor-distal immune suppression promotes tumor growth by preventing the recruitment of leukocytes to the tumor-proximal microenvironment. Tumor necrosis factor (TNF)-a is both secreted by and expressed on the cell-surface (mTNF-a) of macrophages. When stimulated with LPS, tumor-burdened host (TBH) macrophages secrete more TNF-a than normal host (NH) macrophages. In this study, I showed that mTNF-a is elevated both in freshly isolated and stimulated TBH macrophages. Additionally, I analyzed the expression of Fas and FasL on freshly isolated and LPS-stimulated macrophages and found no differences between TBH and NH macrophages. Fas and Fas ligand (FasL) cell-surface expression was analyzed on NH and TBH T-cells. While no difference was observed in freshly isolated cells, cell-surface expression of both proteins remained higher in TBH T-cells than NH T-cells after mitogenic stimulation. Fas and FasL analysis was also extended to the MethKDE fibrosarcoma and I found that these tumor cells express high levels of FasL. Because past observations show increased TNF-a mRNA expression in TBH macrophages relative to NH macrophages, I hypothesized that NF-kB activation may be increased as well. NF-kB is a transcription factor whose activation is required for TNF-a transcription. I observed increased NF-kB activation in both splenic and peritoneal TBH macrophages. Interestingly, electrophoretic mobility shift analysis (EMSA) suggests that different species of NF-kB were found in each distinct population of macrophages. Together, these data demonstrate that cell-surface tumoricidal molecules and NF-kB are dysregulated in the tumor-burdened host.en
dc.description.degreeMaster of Scienceen
dc.format.mediumETDen
dc.identifier.otheretd-07022002-152228en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-07022002-152228en
dc.identifier.urihttp://hdl.handle.net/10919/9609en
dc.publisherVirginia Techen
dc.relation.haspartMichaelMcConnellFINAL.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectFasen
dc.subjectmTNF-aen
dc.subjectMethKDE fibrosarcomaen
dc.subjectNF-kBen
dc.subjectFasLen
dc.titleCell-surface Tumoricidal Molecules and NF-kB in the Tumor-burdened Hosten
dc.typeThesisen
thesis.degree.disciplineBiologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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