Mathematical Modeling of Melanoma Cell Migration with an Elastic Continuum Model for the Evaluation of the Influence of Tumor Necrosis Factor-Alpha on Migration
An elastic continuum mathematical model was implemented to study collective C8161 melanoma cell migration during a “scratch wound” assay, in control and under the influence of the proinflammatory cytokine tumour necrosis factor-alpha (TNF-α). The model has four constants: force that results from lamellipod formation (F), adhesion constant between cells and extracellular matrix (ECM) (b), cell layer elasticity modulus (k), and growth rate (ρ). A nonlinear regression routine was used to obtain the parameters of the model with data from an experiment made with C8161 melanoma cells, with and without TNF-α. Coefficient of determination for both situations was and , respectively. The parameters values obtained were similar to the ones found in the literature. However, the adhesion constant value decreased with the introduction of TNF-α, which is not in accordance with expected since the presence of TNF-α is associated with an increased expression of integrins that would promote an enhanced adhesion among cells. The model was used in a study relating to the adhesion constant and cell migration, and the results suggested that cell migration decreases with higher adhesion, which is also not in accordance with expected. These differences would not occur if it was considered that TNF-α increases the elasticity modulus of the cell layer. 1. Introduction Skin cancer can be divided in two groups: melanoma and nonmelanoma. Melanoma initiates with an alteration in melanocytes, skin cells that produce melanin [1]. According to the World Health Organization data, there are worldwide currently 2 to 3 million nonmelanoma cases and 132 thousand melanoma cases. Although melanoma represents around 5% of total occurrences, it is responsible for most deaths of this type of cancer [2]. Melanoma has a radial growth phase that occurs in the epidermis. Radial growth phase cells can progress to vertical growth phase [3], in which cells grow beyond basal layer into the dermis, a vascularized region. Melanomas in radial growth phase can be surgically removed with high success rates, unlike vertical growth phase melanomas, which can become metastatic and have poor prognosis [4]. When melanoma is detected within initial stages, survival rate is of approximately 98%, decreasing to 16% in melanoma advanced stages [2]. Studies have shown a relationship between inflammatory processes and the appearance and development of different types of cancer, as well as lower incidence and mortality of several types of cancer through treatment with nonsteroidal anti-inflammatory agents [5–7]. During
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