The role of Fas ligand in the cross-talk of tumor cells and fibroblasts during tumor encapsulation
| Autor: | Jia-YingHung, 洪家瑩 |
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| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 103 Stromal cells in the tumor microenvironment play an important role in cancer development. Cancer associated fibroblasts make up the bulk of cancer stroma and contribute to create a tumor-promoting microenvironment for cancer initiation, angiogenesis, invasion, and metastasis. Fas ligand (FasL), the conventional ligand of Fas, is widely expressed in a variety of cancers. Fas/FasL interaction induces signal for program cell death that not only regulates the homeostasis of immune system, but also participates in the progression of cancer. It was reported FasL expression correlates with malignancy and metastasis. Our previous studies showed that tumor nodules were encapsulated by fibroblast-like cells when FasL was knocked down. We hypothesize that the level of FasL expression in tumor cells can affect tumor nodule architecture and the interaction between tumor cells and fibroblasts leading to metastasis or immune evasion. To determine the correlation of FasL and tumor encapsulation by fibroblasts, we co-cultured various tumor cell lines with human primary fibroblasts. Tumor cells with low expression level of FasL could be well-encapsulated by fibroblasts while those with high expression level of FasL could not but cross over fibroblasts. To investigate the role of FasL in tumor-fibroblasts interaction, we down-regulated the FasL of U118 and B16F10 cell by FasL-ribozyme (FasL-RZ). Down-regulation of FasL had increased the percentage of tumor cells encircled by fibroblasts. We further performed invasion assay by using µ-dish culture-insert. We observed that FasL enhanced tumor cell invasion into a culture of fibroblasts. On the other hand, conditioned medium from FasLhigh tumor cells could attract more fibroblasts and induced fibroblasts activation. Collectively, FasL can induce tumor invasion, inhibit tumor encapsulated by fibroblasts, and avtivate fibroblasts. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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