Details
- Autor(en) / Beteiligte
- Titel
- Reoxygenation from chronic hypoxia promotes metastatic processes in pancreatic cancer through the Hedgehog signaling
- Ist Teil von
- Cancer science, 2014-03, Vol.105 (3), p.324-333
- Ort / Verlag
- England: BlackWell Publishing Ltd
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- Wiley Online Library - AutoHoldings Journals
- Beschreibungen/Notizen
- Pancreatic ductal adenocarcinoma (PDAC) is among the most deadly types of malignancies because of its high ability to metastasize. PDAC is thought to be under hypoxic condition. Therefore, to investigate the mechanism of metastatic processes, chronic‐hypoxia‐resistant PDAC cells were newly generated under hypoxic condition for 3–6 months and reoxygenation experiments were performed using these chronic‐hypoxia‐resistant PDAC cells in in vivo‐mimicking conditions. Proliferation, invasiveness and tumorigenicity in PDAC cells were significantly increased by reoxygenation. A Hedgehog (Hh) signaling component, Gli1, was significantly increased by reoxygenation. Gli1 knockdown inhibited reoxygenation‐induced increases in proliferation and tumorigenicity and decreased invasiveness through suppression of matrix metalloproteinase (MMP) 2 and MMP9. Moreover, inhibition of Sonic Hh and Smoothened abrogated reoxygenation induced increases in proliferation and invasiveness. These results suggest that metastatic processes in PDAC are induced through activation of the Hh signaling pathway. Therefore, the Hh signaling pathway may be a therapeutic target for refractory PDAC in metastatic processes induced by reoxygenation. Reoxygenation from chronic hypoxia enhances expression of GLI1, a marker of Hedgehog signal activation. Ac‐H cells, Acute‐hypoxic cells; Ch‐H‐R cells, Chronic‐hypoxia‐resistant cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1347-9032eISSN: 1349-7006DOI: 10.1111/cas.12348Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4317936
- Format
- –
- Schlagworte
- Animals, Carcinoma, Pancreatic Ductal - metabolism, Carcinoma, Pancreatic Ductal - secondary, Cell Hypoxia, Cell Line, Tumor, Female, Hedgehog, Hedgehog Proteins - metabolism, Humans, invasiveness, Matrix Metalloproteinase 2 - metabolism, Matrix Metalloproteinase 9 - metabolism, Mice, Mice, Inbred BALB C, Mice, Nude, Original, Oxygen - metabolism, pancreatic cancer, Pancreatic Neoplasms - metabolism, Pancreatic Neoplasms - pathology, proliferation, Receptors, G-Protein-Coupled - metabolism, reoxygenation, Signal Transduction, Smoothened Receptor, Transcription Factors - metabolism, Zinc Finger Protein GLI1