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Correlation of TGF-β1 and oxidative stress in the blood of patients with melanoma: a clue to understanding melanoma progression?

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Tumor Biology

Abstract

TGF-β1 and oxidative stress are involved in cancer progression, but in melanoma, their role is still controversial. Our aim was to correlate plasma TGF-β1 levels and systemic oxidative stress biomarkers in patients with melanoma, with or without disease metastasis, to understand their participation in melanoma progression. Thirty patients were recruited for melanoma surveillance, together with 30 healthy volunteers. Patients were divided into two groups: Non-metastasis, comprising patients with tumor removal and no metastatic episode for 3 years; and Metastasis, comprising patients with a metastatic episode. The plasmatic cytokines TGF-β1, IL-1 β, and TNF-α were analyzed by ELISA. For oxidative stress, the following assays were performed: malondialdehyde (MDA), advanced oxidation protein products (AOPP) levels, total radical-trapping antioxidant parameter (TRAP) and thiol in plasma, and lipid peroxidation, SOD and catalase activity and GSH in erythrocytes. Patients with a metastatic episode had less circulating TGF-β1 and increased TRAP, thiol, AOPP and lipid peroxidation levels. MDA was increased in both melanoma groups, while catalase, GSH, and IL-1β was decreased in Non-metastasis patients. Significant negative correlations were observed between TGF-β1 levels and systemic MDA, and TGF-β1 levels and systemic AOPP, while a positive correlation was observed between TGF-β1 levels and erythrocyte GSH. Lower levels of TGF-β1 were related to increased oxidative stress in Metastasis patients, reinforcing new evidence that in melanoma TGF-β1 acts as a tumor suppressor, inhibiting tumor relapse. These findings provide new knowledge concerning this cancer pathophysiology, extending the possibilities of investigating new therapies based on this evidence.

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Acknowledgments

The authors are grateful to J.A. Vargas and P. S. R. D. Filho for their excellent technical assistance and E. C. B. Carmelo of the Department of Clinical Research of the Londrina Cancer Hospital for her important assistance in patient recruitment and interview. The authors would also like to thank physicians M. A. Buges and C. Z. Campos for allowing their patients to participate in the study. The authors also thank the Araucária Foundation for providing financial support.

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Authors and Affiliations

  1. Laboratory of Molecular Pathology, Londrina State University (UEL), Londrina, Paraná, Brazil

    Sara Santos Bernardes, Fernando Pinheiro de Souza-Neto, Gabriella Pasqual Melo, Poliana Camila Marinello & Alessandra L. Cecchini

  2. Laboratory of the Pathophysiology of Muscle Adaptations, Londrina State University (UEL), Londrina, Paraná, Brazil

    Flávia Alessandra Guarnier

  3. Laboratory of Pathophysiology and Free Radicals, Londrina State University (UEL), Londrina, Paraná, Brazil

    Rubens Cecchini

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  1. Sara Santos Bernardes
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Correspondence to Alessandra L. Cecchini.

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Santos Bernardes, S., de Souza-Neto, F.P., Pasqual Melo, G. et al. Correlation of TGF-β1 and oxidative stress in the blood of patients with melanoma: a clue to understanding melanoma progression?. Tumor Biol. 37, 10753–10761 (2016). https://doi.org/10.1007/s13277-016-4967-4

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