Cancer Microenvironment

, Volume 5, Issue 1, pp 73–82

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

  • Kyoko Kushiro
  • Randy A. Chu
  • Akanksha Verma
  • Nomelí P. Núñez
Original Paper

DOI: 10.1007/s12307-011-0087-2

Cite this article as:
Kushiro, K., Chu, R.A., Verma, A. et al. Cancer Microenvironment (2012) 5: 73. doi:10.1007/s12307-011-0087-2

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.

Keywords

3T3L1 adipocytesB16BL6EMTSnai1Kiss1

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Kyoko Kushiro
    • 1
  • Randy A. Chu
    • 2
  • Akanksha Verma
    • 2
  • Nomelí P. Núñez
    • 1
    • 3
  1. 1.Institute for Cellular and Molecular BiologyUniversity of Texas at AustinAustinUSA
  2. 2.School of Biological SciencesUniversity of Texas at AustinAustinUSA
  3. 3.Department of Nutritional SciencesThe University of Texas at AustinAustinUSA