Hypoxia Enhances Aggressiveness of Cholangiocarcinoma Cells


Hypoxia, a common feature of solid tumors, plays a significant role in determining tumor phenotype andtumor progression. In this study, using an in-house PCR-array, we investigated phenotypic changes anddifferentially expressed hypoxia related genes in the KKU-M213 CCA cell line, cultured under hypoxic (1% O2)condition. Trefoil factor-1 (TFF1), a disintegrin, and metalloprotease 12 (ADAM12), integrin-alpha 5 (ITGA5)and baculoviral IAP repeat-containing 5 (BIRC5/survivin), proteins involved with cell proliferation, metastasisand apoptosis resistance, were up-regulated whereas uridine 5’-monophosphate synthase (UMPS) and S100calcium binding protein P (S100P), involved with chemosensitivity and cell adhesion, were down-regulated.Growth arrest, apoptosis resistance to UV-irradiation and chemotherapeutic drugs (5- flourouracil, cisplatin,doxorubicin) as well as cell adhesion were thus significantly enhanced upon exposure to hypoxic condition. Thesefindings emphasize the significance of a hypoxic state in the induction of an aggressive phenotype and suggestthe potential of targeting hypoxia regulated genes to enhance the sensitivity of chemotherapeutic drug againstCCA.