Reoxygenation from chronic hypoxia promotes metastatic processes in pancreatic cancer through the Hedgehog signaling.
Bottom Line: Proliferation, invasiveness and tumorigenicity in PDAC cells were significantly increased by reoxygenation.A Hedgehog (Hh) signaling component, Gli1, was significantly increased by reoxygenation.These results suggest that metastatic processes in PDAC are induced through activation of the Hh signaling pathway.
Affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Show MeSH
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Mentions: To confirm the observed increase in proliferation by reoxygenation in vitro, we investigated the tumorigenicity of reoxygenated Ch-H-R cells. Normal PDAC cells cultured under normoxia were used as a control in this experiment. Anchorage-independent proliferation in reoxygenated Ch-H-R cells was significantly higher than that in wild type PDAC cells (Fig.5a). Tumors from mice administered with reoxygenated Ch-H-R cells were significantly larger than those from mice injected with wild-type cells (Fig.5b). Gli1 positive cells in tumors from mice injected with reoxygenated Ch-H-R cells were significantly higher than those in the controls (Fig.5c). Next, the effect of Hh signaling in increased tumorigenicity by reoxygenation was examined. Anchorage-independent proliferation in Gli1 siRNA transfected-reoxygenated Ch-H-R cells was significantly lower than that in the control (Fig.5d) in vitro. In vivo, tumors from mice injected with Gli1 siRNA-transfected-reoxygenated Ch-H-R cells were significantly smaller than those from mice injected with control siRNA-transfected cells (Fig.5e). These results suggest that Gli1 plays a pivotal role in tumorigenicity in reoxygenation in vivo.
Affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.