The microenvironment for EBV-N-LMP1 tumor progression and the in vitro tunnel activity of tumor-associated macrophage
| Autor: | Yu Fen Huang, 黃育芬 |
|---|---|
| Rok vydání: | 2009 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 97 Nasopharyngeal carcinoma (NPC) is an unique cancer endemic in South China and Taiwan. And the Epstein-Barr virus-encoded oncogene latent membrane protein- 1 (N-LMP1) is considered as the major promoter in NPC development. To understand the pathogenesis of LMP1, we have established an N-LMP1 tumor mouse model. In the model, this study is focused to analyse the gene expression of various immune and angiogenic factors along tumor progression by RT-PCR. In addition, we developed an in vitro tunnel assay to mimic the angiogenic property of TAM, making tunnels in stroma during tumor angiogenesis. In the RT-PCR study, we found both CD11b and F4/80 (markers of TAM) are consistency expressed, indicating it may be the major population of the infiltrated leukocytes. CD4 is rare, but NK detected by NK1.1 is relatively at higher expression level. IL-1β is stably expressed and IL-10 is rare. CCL2/CCR2, CCL3/CCR1, CCR5 and IP10 all exit in N-LMP1 tumor. We also found stable expression of CD31 and VEGF/VEGFR2. The expression of Ang1/Tie2 is more evident on day 21 and 28. Compare to the tumor becoming non angiogenic in the immunized mice, the apparent differences are the increase of CD4, NK and IL12, and the decrease of CD31. The data suggested that N-LMP1 tumor angiogenesis and progression is complex process heavily involved with various immune cells and factors. In the tunnel assay, we have developed optimal conditions for in vitro tunnel assay and used TAM for a preliminary test. We found that TAM alone could penetrate the matrigel, and the addition of neutratizing anti-CCL3 antibody would greatly reduce the ability. Therefore, CCL3 may be involved in the control of TAM to degrade matrix. The regulatory mechanism through chemokine system warrants further investigation. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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