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Adipocytes Promote B16BL6 Melanoma Cell Invasion and the Epithelial-to-Mesenchymal Transition

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Cancer Microenvironment

Abstract

Metastatic melanoma is one of the most deadly and evasive types of cancer. On average, cancer patients with metastatic melanoma survive only 6–9 months after diagnosis. Epidemiological and animal studies suggest that obesity increases the metastatic ability of malignant melanoma, though the mechanism is not known. In the present studies, we assessed the ability of 3T3L1 adipocytes to modulate B16BL6 melanoma cell invasion and the Epithelial-to-Mesenchymal Transition (EMT). For this purpose, we induced the differentiation of 3T3L1 fibroblasts to adipocytes. Then, we collected the cell culture media from both fibroblasts and adipocytes and determined their effect on the invasive ability and EMT gene expression of B16BL6 melanoma cells. Results show that adipocyte media increased that ability of B16BL6 cells to invade. The higher invasive ability of B16BL6 melanoma cells was associated with increased expression of EMT genes such as Snai1, MMP9, Twist, and Vimentin. Additionally, the expression of the cell-to-cell adhesion protein E-cadherin and the metastasis suppressor gene Kiss1 were down-regulated in these B16BL6 cells. Also, adipocytes had high levels of the pro-inflammatory cytokine Interleukin 6 (IL-6). Treatment of B16BL6 cells with IL-6 elicited similar effects as the adipocyte media; IL-6 promoted the invasive ability of B16BL6 melanoma cells, increased the expression of Snai1, and decreased Kiss1 expression. IL-6 neutralization, however, did not have a visible effect on adipocyte media-induced invasion and snai1 staining. In summary, adipocytes may increase the invasive ability of B16BL6 melanoma cells by promoting EMT and decreasing the expression of genes such as E-cadherin and Kiss1.

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Acknowledgement

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 Institute grant NCI 1K22CA127519-01A1 and National Institute of Environmental Health Sciences Center grants ES09145 and ES007784.

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The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USA

    Kyoko Kushiro & Nomelí P. Núñez

  2. School of Biological Sciences, University of Texas at Austin, Austin, TX, USA

    Randy A. Chu & Akanksha Verma

  3. 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. Randy A. Chu
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Correspondence to Nomelí P. Núñez.

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Kushiro, K., Chu, R.A., Verma, A. et al. Adipocytes Promote B16BL6 Melanoma Cell Invasion and the Epithelial-to-Mesenchymal Transition. Cancer Microenvironment 5, 73–82 (2012). https://doi.org/10.1007/s12307-011-0087-2

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  • DOI: https://doi.org/10.1007/s12307-011-0087-2

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