Expression of E-selectin ligand-1 (CFR/ESL-1) on hepatic stellate cells: implications for leukocyte extravasation and liver metastasis
| Autor: | Axel M. Gressner, Paul Kiefer, Carmen G. Tag, Marianne Antoine, Claus Hellerbrand |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research Angiogenesis Sialoglycoproteins Cell Blotting Western Fluorescent Antibody Technique Gene Expression Inflammation Biology Rats Sprague-Dawley medicine Hepatic Stellate Cells Animals Humans RNA Messenger Neoplasm Metastasis Reverse Transcriptase Polymerase Chain Reaction Transdifferentiation Liver Neoplasms General Medicine Blotting Northern Fucosyltransferases Leukocyte extravasation Receptors Fibroblast Growth Factor Liver regeneration Cell Hypoxia Rats Chemotaxis Leukocyte medicine.anatomical_structure Oncology Fibroblast growth factor receptor Hepatic stellate cell Cancer research medicine.symptom E-Selectin |
| Zdroj: | Oncology reports. 21(2) |
| ISSN: | 1021-335X |
| Popis: | Leukocytes and tumor cells use E-selectin binding ligands to attach to activated endothelial cells expressing E-selectin during inflammation or metastasis. The cysteine-rich fibroblast growth factor receptor (CFR) represents the main E-selectin ligand (ESL-1) on granulocytes and its expression is exclusively modified by alpha(1,3)-fucosyltransferases IV or VII (FucT4 and FucT7). Hepatic stellate cells (HSC) are pericytes of liver sinusoidal endothelial cells. The activation of HSC and transdifferentiation into a myofibroblastic phenotype is involved in the repair of liver tissue injury, liver regeneration and angiogenesis of liver metastases. In the present study, we demonstrated that HSC expressed CFR together with FucT7 and exhibited a functional E-selectin binding activity on their cell surface. Since HSC appear to be oxygen-sensing cells, the expression of E-selectin binding activity was analyzed in HSC under a hypoxic atmosphere. While the expression of the glycoprotein CFR was unaffected by hypoxia, the cell-associated E-selectin binding activity decreased. However, under the same conditions, mRNA expression of the modifying enzyme FucT7 increased. The loss of E-selectin binding activity, therefore, appears to be neither the result of a reduced expression of the modifying transferase nor the expression of the backbone glycoprotein. After the transient transfection of HSC with CFR cDNA, the E-selectin binding activity (ESL-1) was efficiently released into the supernatant. Therefore, we hypothesize that under hypoxia, ESL-1 is shed from activated HSC. Our findings provide a novel perspective on the function of HSC in liver metastasis and inflammatory liver diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|