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Ob/ob serum promotes a mesenchymal cell phenotype in B16BL6 melanoma cells

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Abstract

In 2009, malignant melanoma was responsible for approximately 9,000 deaths in the US. These deaths are often associated with aggressive metastasis to secondary sites such as the lungs. Epidemiological and animal studies suggest that obesity is a risk factor for melanoma. Others have shown that B16BL6 melanoma cells metastasize more aggressively in obese ob/ob than in lean mice. However, the mechanism by which obesity promotes B16BL6 melanoma metastasis in ob/ob mice has not been identified. In the present study, we used serum obtained from control and ob/ob leptin-deficient obese mice to determine if obese serum increases the aggressive phenotype of melanoma cells. Results showed that ob/ob serum has higher levels of resistin, insulin, tPAI1, IL-6, TNF-α, and MCP-1 compared to control serum. We showed that ob/ob serum increases the invasive ability of B16BL6 melanomas. To further determine the mechanism by which ob/ob serum increases the invasive ability of melanomas, we determined the effect of ob/ob and control serum on genes associated with the epithelial-to-mesenchymal transition (EMT). Cancer cells with a mesenchymal phenotype have a higher metastatic ability. Snai1 and Twist are genes that are strongly associated with EMT and metastasis of melanomas. Our results showed that ob/ob serum increases the expression of Snai1 and Twist. Moreover, ob/ob serum increased matrix metalloproteast 9 (MMP9) activity and decreased the expression of E-cadherin and the metastasis suppressor gene Kiss1. In summary, results suggest that obesity may increase the metastatic ability of melanoma by promoting a mesenchymal cell phenotype.

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Acknowledgements

This work was supported by the American Cancer Society grant ACS RSG CNE-113703 and by grants from the National Institutes of Health: National Cancer Society grant NCI 1K22CA127519-01A1 and National Institute of Environmental Health Sciences Center grants ES09145 and ES007784.

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Authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. The University of Texas at Austin, Institute for Cellular and Molecular Biology, 1 University Station, 1 A4800, Austin, TX, 78712-0160, USA

    Kyoko Kushiro & Nomelí P. Núñez

  2. Institute for Cellular and Molecular Biology, and Department of Nutritional Sciences, The University of Texas at Austin, 1 University Station, A2703, Austin, TX, 78712, USA

    Nomelí P. Núñez

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  1. Kyoko Kushiro
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  2. Nomelí P. Núñez
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Correspondence to Nomelí P. Núñez.

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Kushiro, K., Núñez, N.P. Ob/ob serum promotes a mesenchymal cell phenotype in B16BL6 melanoma cells. Clin Exp Metastasis 28, 877–886 (2011). https://doi.org/10.1007/s10585-011-9418-4

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  • DOI: https://doi.org/10.1007/s10585-011-9418-4

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