Transforming Growth Factor Beta-Induced (TGFBI) Is an Anti-Adhesive Protein Regulating the Invasive Growth of Melanoma Cells
| Autor: | Johanna Soikkeli, Erkki Hölttä, Olli Saksela, Pirjo Nummela, Johanna Lammi, Pirjo Laakkonen |
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| Rok vydání: | 2012 |
| Předmět: |
Talin
Pathology medicine.medical_specialty Mice Nude Biology Periostin Pathology and Forensic Medicine Extracellular matrix Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Transforming Growth Factor beta Cell Adhesion Tumor Cells Cultured medicine Animals Humans Neoplasm Invasiveness Melanoma Skin 030304 developmental biology Extracellular Matrix Proteins Mice Inbred BALB C 0303 health sciences Matrigel Integrin beta1 Transforming growth factor beta Fibroblasts medicine.disease Recombinant Proteins eye diseases Extracellular Matrix Neoplasm Proteins Up-Regulation Gene Expression Regulation Neoplastic Thymosin Fibronectin Actin Cytoskeleton Gene Knockdown Techniques 030220 oncology & carcinogenesis biology.protein Cancer research Female Neoplasm Transplantation Genome-Wide Association Study TGFBI Transforming growth factor |
| Zdroj: | The American Journal of Pathology; Vol 180 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2011.12.035 |
| Popis: | Melanoma is a malignancy characterized by high invasive/metastatic potential, with no efficient therapy after metastasis. Understanding the molecular mechanisms underlying the invasive/metastatic tendency is therefore important. Our genome-wide gene expression analyses revealed that human melanoma cell lines WM793 and especially WM239 (vertical growth phase and metastatic cells, respectively) overexpress the extracellular matrix (ECM) protein transforming growth factor β induced (TGFBI). In adhesion assays, recombinant TGFBI was strongly anti-adhesive for both melanoma cells and skin fibroblasts. TGFBI further impaired the adhesion of melanoma cells to the adhesive ECM proteins fibronectin, collagen-I, and laminin, known to interact with it. Unexpectedly, WM239 cells migrated/invaded more effectively in three-dimensional collagen-I and Matrigel cultures after knockdown of TGFBI by shRNA expression. However, in the physiological subcutaneous microenvironment in nude mice, after TGFBI knockdown, these cells showed markedly impaired tumor growth and invasive capability; the initially formed small tumors later underwent myxoid degeneration and completely regressed. By contrast, the expanding control tumors showed intense TGFBI staining at the tumor edges, co-localizing with the fibrillar fibronectin/tenascin-C/periostin structures that characteristically surround melanoma cells at invasion fronts. Furthermore, TGFBI was found in similar fibrillar structures in clinical human melanoma metastases as well, co-localizing with fibronectin. These data imply an important role for TGFBI in the ECM deposition and invasive growth of melanoma cells, rendering TGFBI a potential target for therapeutic interventions. |
| Databáze: | OpenAIRE |
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