Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Helige, C; Hofmann-Wellenhof, R; Fink-Puches, R; Smolle, J.
Mofarotene-induced inhibition of melanoma cell motility by increasing vinculin-containing focal contacts.
MELANOMA RES. 2004; 14(6): 547-554.
Doi: 10.1097%2F00008390-200412000-00018
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- Führende Autor*innen der Med Uni Graz
- Helige Christine
- Co-Autor*innen der Med Uni Graz
- Fink-Puches Regina
- Hofmann-Wellenhof Rainer
- Smolle Josef
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- Abstract:
- Tumour cell motility, which is dependent on the organization of the cytoskeleton, is considered to play an important role in the spread of malignant melanoma. Therefore, retinoids, which are modulators of cytoskeletal organization, may affect the motile activity of melanoma cells. In this study, the effects of the arotinoid mofarotene on single cell motility and vinculin organization of the highly metastatic melanoma cell line K-1735-M2 were determined. Melanoma cells were cultivated in a temperature- and CO2-controlled microincubator, which was located on the microscope stage. Cell movements were evaluated quantitatively from time-lapse video recordings using an IBAS image analysis system. Vinculin distribution was evaluated using confocal laser scanning microscopy and a specially developed computerized image analysing program. In addition, melanoma cell invasion was tested on the embryonic chick heart model. Although 10 microM mofarotene did not reduce the translocative movements of melanoma cells, it significantly inhibited stationary motility, including fast plasma membrane movements and changes in shape. Mofarotene also showed a pronounced effect on the organization of vinculin-containing cell-substratum adhesion plaques. In retinoid-treated cells, the numbers of vinculin plaques per cell, and particularly those in the marginal areas of the cells, were significantly increased compared with untreated controls. Furthermore, the compound reduced the invasiveness of melanoma cells in a three-dimensional tissue culture model. In conclusion, our data demonstrate that mofarotene, an already almost forgotten synthetic retinoid, shows interesting effects on melanoma cells, which may be relevant for a slowdown of tumour spread.
- Find related publications in this database (using NLM MeSH Indexing)
- Actins - metabolism
- Animals - metabolism
- Cell Adhesion - drug effects
- Cell Movement - drug effects
- Chick Embryo - drug effects
- Chickens - drug effects
- Collagen - metabolism
- Drug Combinations - metabolism
- Focal Adhesions - drug effects
- Heart - drug effects
- Laminin - metabolism
- Lung Neoplasms - drug therapy
- Melanoma, Experimental - drug therapy
- Mice - drug therapy
- Morpholines - pharmacology
- Neoplasm Invasiveness - pathology
- Proteoglycans - metabolism
- Retinoids - pharmacology
- Skin Neoplasms - pharmacology
- Spheroids, Cellular - drug effects
- Tumor Cells, Cultured - drug effects
- Vinculin - metabolism
- Find related publications in this database (Keywords)
- cell motility
- computerized image analysis
- melanoma
- melanoma cell invasion
- retinoids
- vinculin organization