| Type of Document |
Master's Thesis |
| Author |
McConnell, Michael James
|
| URN |
etd-07022002-152228 |
| Title |
Cell-surface Tumoricidal Molecules and NF-kB in the Tumor-burdened Host |
| Degree |
Master of Science |
| Department |
Biology |
| Advisory Committee |
| Advisor Name |
Title |
| Elgert, Klaus D. |
Committee Chair |
| Rutherford, Charles L. |
Committee Member |
| Winkel, Brenda S. J. |
Committee Member |
|
| Keywords |
- Fas
- mTNF-a
- MethKDE fibrosarcoma
- NF-kB
- FasL
|
| Date of Defense |
2002-06-24 |
| Availability |
unrestricted |
Abstract
Tumor-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.
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| Files |
| Filename |
Size |
Approximate Download Time
(Hours:Minutes:Seconds)
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| 28.8 Modem |
56K Modem |
ISDN (64 Kb) |
ISDN (128 Kb) |
Higher-speed Access |
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MichaelMcConnellFINAL.pdf |
1.42 Mb |
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