Increased plasticity of the stiffness of melanoma cells correlates with their acquisition of metastatic properties

The stiffness of tumor cells varies during cancer progression. In particular, metastatic carcinoma cells analyzed by Atomic Force Microscopy (AFM) appear softer than non-invasive and normal cells. Here we examined by AFM how the stiffness of melanoma cells varies during progression from non-invasive Radial Growth Phase (RGP) to invasive Vertical Growth Phase (VGP) and to metastatic tumors. We show that transformation of melanocytes to RGP and to VGP cells is characterized by decreased cell stiffness. However, further progression to metastatic melanoma is accompanied by increased cell stiffness and the acquisition of higher plasticity by tumor cells, which is manifested by their ability to greatly augment or reduce their stiffness in response to diverse adhesion conditions. We conclude that increased plasticity, rather than decreased stiffness as suggested for other tumor types, is a marker of melanoma malignancy. These findings advise caution about the potential use of AFM for melanoma diagnosis.From the Clinical EditorThis study investigates the changes to cellular stiffness in metastatic melanoma cells examined via atomic force microscopy. The results demonstrate that increased plasticity is a marker of melanoma malignancy, as opposed to decreased stiffness.

Graphical AbstractTransformation of RGP melanoma into VGP melanoma is characterized by decreased cell stiffness (a) which can augment cell deformability and promote invasion. Metastatic spreading implicates cell survival in the circulation, extravasation (b), and growth in distant tissues (c) and requires that melanoma cells vary their cytoarchitecture and consequently further reduce or increase their stiffness in order to adapt to different environments. Hence, metastatic melanomas are characterized by high plasticity, defined as the ability of tumor cells to respond and adjust their stiffness to variable external conditions (d). High plasticity, rather than decreased stiffness as for other tumor types, is a marker of melanoma malignancy.Figure optionsDownload high-quality image (159 K)Download as PowerPoint slide