Up-regulation of 12(S)-lipoxygenase induces a migratory phenotype in colorectal cancer cells
| Autor: | P. Krieg, W. Bednar, D. Massudom, Gerhard Fürstenberger, M. Klimpfinger, I. Kalny, Lukas F. Mager, E. Bogner, T. Klampfl, Walter Berger, Brigitte Marian, Christine Heinzle, Josef Karner, Stefan Stättner |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
LOX
lipoxygenase Angiogenesis Colorectal cancer Lipoxygenase Cell AA arachidonic acid Integrin Inflammation Biology Arachidonate 12-Lipoxygenase 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation HETE hydroxyeicosatetraenic acid Cell Movement Tumor Cells Cultured medicine Humans Cell migration 12-Hydroxy-5 8 10 14-eicosatetraenoic Acid 030304 developmental biology 0303 health sciences integumentary system Malignant phenotype E-cadherin 12(S)-HETE Cell Biology medicine.disease Up-Regulation Phenotype medicine.anatomical_structure Caco-2 Cell culture 030220 oncology & carcinogenesis Immunology Cancer research lipids (amino acids peptides and proteins) Caco-2 Cells medicine.symptom Colorectal Neoplasms Research Article |
| Zdroj: | Experimental Cell Research |
| ISSN: | 0014-4827 |
| Popis: | 12(S)-Lipoxygenase (LOX) and its product 12(S)-hydroxyeicosatetraenic (HETE) acid have been implicated in angiogenesis and tumour invasion in several tumour types while their role in colorectal cancer progression has not yet been studied. We have analysed 12(S)-LOX expression in colorectal tumours and found gene expression up-regulated in colorectal cancer specimens for which the pathology report described involvement of inflammation. Using cell line models exposed to 12(S)-HETE or over-expressing 12(S)-LOX malignant cell growth as well as tumour cell migration was found to be stimulated. Specifically, Caco2 and SW480 cells over-expressing 12(S)-LOX formed fewer colonies from sparse cultures, but migrated better in filter-migration assays. SW480 LOX cells also had higher anchorage-independent growth capacity and a higher tendency to metastasise in vivo. Knock-down or inhibition of 12(S)-LOX inhibited cell migration and anchorage-independent growth in both 12(S)-LOX transfectants and SW620 cells that express high endogenous levels of 12(S)-LOX. On the cell surface E-cadherin and integrin-β1 expression were down-regulated in a 12(S)-LOX-dependent manner disturbing cell–cell interactions. The results demonstrate that 12(S)-LOX expression in inflammatory areas of colorectal tumours has the capacity to induce an invasive phenotype in colorectal cancer cells and could be targeted for therapy. Highlights ► 12(S)-LOX is up-regulated in inflammatory areas of colorectal tumours. ► 12(S)-HETE and 12(S)-LOX over-expression stimulate malignant growth and migration. ► 12(S)-LOX over-expressing SW480 cells have a higher tendency to metastasise. ► Blocking 12(S)-LOX activity or expression inhibits malignant growth and migration. |
| Databáze: | OpenAIRE |
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