Crosstalk between autophagy and iron in melanoma progression

Introduction.Autophagy, a catabolic process of protein and organelle recycling by transferring defective cytoplasm and organelles into double-membraned vesicles to degrade and regenerate materials, plays a critical role in maintaining energy homeostasis. Inefficiency chemo-and radiotherapy is largely associated with the activation of autophagy. Among the metals needed by the living organism, iron occupies a special place. The rapid growth of malignant tumors requires much more iron than the metabolism of normal cells.

Objective.To elucidate the relationship between autophagy and iron in melanoma progression.

Materials and methods.In this study we used 2D- and 3D-culturing of melanoma cells with high expression of CD71 (mel P and mel Z) and low expression of CD71 (mel Gus and mel Ibr), flow cytometry and fluorescence microscopy.

Results.The uptake of iron in cancer cells occurs through translocation of the complex of transferrin/receptor (CD71) in the cytoplasm with subsequent dissociation of iron from the complex. Chelation of iron by deferroxamine in melanoma cells mel P and mel Z reduced the level of autophagy about 2-fold. In the presence of an iron donor ferrum ammonium citrate the level of autophagy increased 2.5- fold. The same correlation was observed in melanoma cells with low expression of CD71. Chelation of iron in melanoma cells with high CD71 expression blocked the formation of capillary-like structures. In the presence of an iron donor the formation of capillary-like structures was also not observed. The same correlation was observed in melanoma cells with low expression of CD71. There was an increase in CD105 expression about 50 ± 5 % and 800 ± 50 % under the condition of iron chelation in melanoma cells with high and low expression of CD71, respectively. Quite unexpectably, iron donor also increased expression of CD105 about 35 ± 4 % and 300 ± 3 % in melanoma cells with high and low expression of CD71, respectively

Conclusions.The activation of autophagy promotes the survival of tumor cells by triggering a number of metabolic functions with the participation of iron.

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