Abstract
Simple SummaryDespite recent advances in therapeutic options, melanoma remains a deadly disease with a poor prognosis. Physical gas plasma has been proposed as a promising technology for the treatment of melanoma. This study aimed to develop and investigate a convenient test system based on three-dimensional cell cultures (spheroids) of two melanoma cell lines in response to physical gas plasma. The experimental approach combined high-content imaging technology and different gas plasma treatment modalities (direct and indirect, gas compositions). Our results revealed that plasma treatment was toxic for both cell lines predominantly dependent on the treatment time. Furthermore, we addressed the question of safety and morphological changes in response to physical gas plasma exposure and found no support for metastatic progression. Treatment with physical gas plasma effectively limited the growth of human 3D melanoma spheroids and provided a versatile test system for more in vivo-like tumor tissue.Melanoma skin cancer is still a deadly disease despite recent advances in therapy. Previous studies have suggested medical plasma technology as a promising modality for melanoma treatment. However, the efficacy of plasmas operated under different ambient air conditions and the comparison of direct and indirect plasma treatments are mostly unexplored for this tumor entity. Moreover, exactly how plasma treatment affects melanoma metastasis has still not been explained. Using 3D tumor spheroid models and high-content imaging technology, we addressed these questions by utilizing one metastatic and one non-metastatic human melanoma cell line targeted with an argon plasma jet. Plasma treatment was toxic in both cell lines. Modulating the oxygen and nitrogen ambient air composition (100/0, 75/25, 50/50, 25/75, and 0/100) gave similar toxicity and reduced the spheroid growth for all conditions. This was the case for both direct and indirect treatments, with the former showing a treatment time-dependent response while the latter resulted in cytotoxicity with the longest treatment time investigated. Live-cell imaging of in-gel cultured spheroids indicated that plasma treatment did not enhance metastasis, and flow cytometry showed a significant modulation of S100A4 but not in any of the five other metastasis-related markers (β-catenin, E-cadherin, LEF1, SLUG, and ZEB1) investigated.
Highlights
Skin cancer, including actinic keratosis, is the most common malignancy in humans, and malignant melanoma has the highest mortality rate
Indirect plasma treatment under ambient air conditions was cytotoxic in MNT-1 (Figure 1b) and SK-MEL-28 (Figure 1c) tumor spheroids in a treatment time-dependent fashion
We experimentally studied the impact of the argon-driven plasma jet kINPen on human melanoma spheroids in relation to the composition of the surrounding gas in the immediate vicinity to the plasma jet, which leads to a modulation of the composition of the reactive species that are eventually transported to the liquids and cells [25,34]
Summary
Skin cancer, including actinic keratosis, is the most common malignancy in humans, and malignant melanoma has the highest mortality rate. Melanoma represents more than 75% of skin cancer-related deaths [1]. Melanomas derive from cutaneous pigment-producing melanocytes that undergo malignant transformation [2]. Due to their close vicinity to the basement membrane and its aggressiveness, the invasion of the dermal layer occurs frequently and worsens the prognosis of patients due to the formation of metastasis elsewhere. The high mortality rate in melanoma patients is due to the high mutation rate, which is frequently accompanied by therapy resistance [3]. Onco-dermatological research aims to find effective therapeutic approaches to tackle this disease
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