Abstract
Oral cancer is a subtype of head and neck cancer. More than 90% of oral cancers are squamous cell carcinomas. Many factors contribute to tumorigenesis including cytokines. Cytokines that produced in the tumor microenvironment plays an important role in cancer pathogenesis. Cancer cells can respond to host-derived cytokines and thus promote tumor growth, attenuate apoptosis and facilitate metastasis. In view of this, we set out to determine whether cytokines would affect the growth of oral cancer cells. We used oral carcinoma 3 (OC3) cell lines, which was established from a long-term areca (betel) chewer who did not smoke, as a cell model. Two invasive lines were used to investigate the mechanism of oral cancer cell invasiveness, OC3-I5 and OC3-IV2 cells. OC3-I5 cells were selected through in-vitro trans-well assays. OC3-IV2 cells were isolated from tumors in lung after tail-vein injection of OC3 to mice. In this study, I showed that the expressions of the interleukin 8 receptors (IL-8Rs) were up-regulated in OC3-I5 cells compare to the other two lines, whereas the mRNA levels of the interleukin 8 (IL-8) among the OC3 cell lines were similar. Understanding the mechanisms by which IL-8 regulates cancer cell growth should shed light on the potential therapeutic strategies for controlling oral cancer cell growth. To this end, I found that OC3 cell lines treated with IL-8 induced phosphorylation of AKT and ERK1/2, but not STAT3. In line with the higher expression of IL-8Rs in OC3-I5 cells, I found that cell proliferation of OC3-I5 cells is more responsive to IL-8 treatment compared to the other two cell lines. The IL-8-enhanced proliferation in part regulated by PI3K-AKT and MEK-ERK1/2 pathways. In contrast, IL-8 treatment did not affect cell migration. Together, findings from this thesis suggest that OC3-I5 cells expressed higher levels of IL-8Rs and are more responsive to IL-8 stimulation which may in turn contribute to increased tumorigenesis of OC3-I5 cells.