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.