Effect of tumor Fas ligand on the spatial distribution and activation of fibroblasts

  • 汪 欣儀

Student thesis: Master's Thesis

Abstract

Tumor infiltrating fibroblasts are a subpopulation of cells in tumor stroma and may promote tumor growth angiogenesis invasion and metastasis Benign tumor nodules are frequently encircled by fibroblast-like cells Fas ligand (FasL) a type II transmembrane protein of the tumor necrosis factor (TNF) family is the authentic ligand of Fas and widely expressed in a variety of cancers Fas/FasL interaction induces signal for cell apoptosis and regulates the homeostasis of immune system The expression of FasL on tumor cells correlates with its malignancy and metastasis Previously we have knocked down the expression of FasL in human glioma by FasL ribozymes (FasL-RZ) and found that the boundary of tumor nodules generated by FasL-RZ cells in Nude mice showed less distinctive boundary between tumor and stromal cells In addition fibroblasts were able to encircle FasLlow tumor cells to form a capsule-like pattern in a 2D co-culture system but not did FasLhigh tumor cells To mimic the interaction between cancer cells and fibroblasts in vivo we applied this study in a three-dimensional (3D) co-culture system to determine the effect of FasL on tumor spheroid architecture FasLhigh tumor cells appeared at the surface of spheroid indicating that they have capability to migrate through fibroblast cell aggregates Accordingly the number of tumor cells on spheroid was reduced when their FasL was suppressed by FasL-RZ transfection Moreover when fibroblasts were cultured in the conditioned media of FasLhigh-tumor cells not only their TGF-β and PDGFA productions but also the activation markers ?-smooth muscle actin (?-SMA) and FAP were significantly elevated Compared with FasLhigh group the activation level of fibroblasts was low after treated with the conditioned media of FasL-RZ cells Taken together our results reveal a role of FasL in determining the architecture of tumor spheroids and the activation of fibroblasts
Date of Award2016 Feb 4
Original languageEnglish
SupervisorBei-Chang Yang (Supervisor)

Cite this

Effect of tumor Fas ligand on the spatial distribution and activation of fibroblasts
欣儀, 汪. (Author). 2016 Feb 4

Student thesis: Master's Thesis