Biophysical and Biochemical Characteristics as Complementary Indicators of Melanoma Progression

Abstract

The multistep character of cancer progression makes it difficult to define a unique biomarker of the disease. Interdisciplinary approaches, combining various complementary techniques, especially those operating at a nanoscale level, potentially accelerate characterization of cancer cells or tissue properties. Here, we study a relation between the surface and biomechanical properties of melanoma cells, measured by mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). In total, seven cell lines have been studied. Six of them were melanoma cells derived from various stages of tumor progression: (1) WM115 cells derived from a 55 year old female skin melanoma at a vertical growth phase (VGP) in the primary melanoma site, (2) WM793 cells established from the vertical growth phase (VGP) of a primary skin melanoma lesion, (3) WM266-4 cells established from a cutaneous skin metastasis detected in the same patient as WM115 cells, (4) WM239 cells derived from a cutaneous skin metastasis, (5) 1205Lu cells originated from a lung metastasis diagnosed in the same patient as WM793 cells, and (6) A375P-cells were derived from a solid malignant tumor located in the lung. As a reference cell line, human epidermal melanocytes from adult skin (primary cell line HEMa-LP) were used. Results reveal low, medium, and large deformability of melanoma cells originating from vertical growth phase (VGP), and skin and lung metastasis, respectively. These changes were accompanied by distinct outcome from principal component analysis (PCA). In relation to VGP melanoma cells, cells from skin and lung metastasis reveal similar or significantly different surface properties. The largest deformability difference observed for cells from VGP and lung metastasis was accompanied by the largest separation of unspecific changes in their surface properties. In this way, we show the evidence that biomechanical and surface biochemical properties of cells change in parallel, indicating a potential of being used as nanobiophysical fingerprints of melanoma progression.

Melanoma in the Eyes of Mechanobiology

“…Therefore, AFM gives thermodynamic and kinetic insights into the effect of DTIC on the CD44 ligand-binding process (Hj et al, 2017). Bobrowska et al (2019) also demonstrated that vertical growth phase melanoma cells showed surface biochemical and biomechanical changes in parallel, which could be used as a fingerprint of melanoma progression (Bobrowska et al, 2019). Nikolovska et al (2017) mentioned that when uronyl-2-O sulfotransferase (Ust) is knocked down in human melanoma cells, the amount of Ust protein is reduced, as well as adhesion and migration of melanoma cells (Nikolovska et al, 2017).…”

Mapping cisplatin-induced viscosity alterations in cancer cells using molecular rotor and fluorescence lifetime imaging microscopy

“…The method has demonstrated applicability for lipidomic analysis for various cancer cells. [35][36][37] The aim of this work was to study cisplatin-induced changes in plasma membrane viscosity using FLIM with BODIPY-based molecular rotor in cancer cells in cell monolayer and multicellular spheroids and correlate them lipid profile, measured with ToF-SIMS, and responsiveness of cells to the treatment. The specific questions we addressed here are: (1) does cisplatin cause any changes in viscosity of cellular plasma membranes when used at therapeutically relevant concentrations; (2) how common are these effects for different cancer cell lines cultured as a monolayer and in multicellular structures; (3) are these changes associated with cell survival and/or cell death; and (4) if membrane lipid composition is the underlying reason for the observed changes in viscosity.…”

Intracellular mechanics and TBX3 expression jointly dictate the spreading mode of melanoma cells in 3D environments

“…It is recognized that the size and deformability of cancer cells may facilitate penetration through several barriers for secondary colonization (Pachenari et al, 2014). However, VGP cells are yet to penetrate thick layers of skin and need mechanical reinforcement to do so (Bobrowska et al, 2019). It is proposed that the deformability of the large VGP cells is insufficient to allow isolated cells to invade the dermis efficiently.…”