Oral communication, CS19 / C89

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Melanocytes and melanoma cells present different mechanical properties that can be modulated by Endothelin 3

The transformation of melanocytes into melanoma cells and the processes of local invasion and metastasis are accompanied by several molecular changes. Although it is clear that these events also require that cells undergo changes in shape and deformation, little has been done to describe the cellular mechanical properties that may underlie these changes and how they may be regulated by signals from the microenvironment. In this study, we evaluated if changes in mechanical properties can be used to distinguish between normal and transformed melanocytes. We adapted a technique generally used in materials engineering, nanoindentation, to compare the elastic storage modulus and membrane rupture load of human primary melanocytes and human melanoma cells cultured on plastic chambers. We found that primary melanocytes are 2.5 times stiffer and 3.5 times harder than melanoma cells. Furthermore, the rupture strength of the cell membrane in primary melanocytes was 2.5 times higher than melanoma cells. These results indicate that melanoma cells are significantly more elastic than normal cells. This difference in elasticity may facilitate the migration and invasion of cancerous cells during metastasis. Previous studies have suggested that the activation of Endothelin receptor b by Endothelin 3 (Edn3) may be involved in melanoma progression by altering the expression of cell adhesion molecules. Therefore, we evaluated the effects of Edn3 on the mechanical properties of primary melanocytes and melanoma cells. Cells were exposed to 1nM of Edn3 for the period of 1, 3 and 5 days. Primary melanocytes showed a gradual decrease in hardness and stiffness as the Edn3 exposure period increased, reaching values similar to those of melanoma cells. Edn3 treated melanoma cells did not show any significant difference in hardness and only a moderate gradual increase in stiffness as the Edn3 exposure period increased. There was no significant difference between the rupture strength of the cell membrane for both types of cells after Edn3 exposure. These results demonstrate that primary melanocytes and melanoma cells modulate their biomechanical properties differentially upon Edn3 exposure. This is the first study to validate the use of nanoindentation as a valuable tool to analyze the differences in mechanical properties of normal and cancerous cells. It also supports the use of cellular biomechanical properties as potential markers of cellular transformation.

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