Breast Cancer Research and Treatment

, Volume 150, Issue 2, pp 255–263 | Cite as

Cancer-mediated adipose reversion promotes cancer cell migration via IL-6 and MCP-1

  • Kaoru Fujisaki
  • Hiroshi Fujimoto
  • Takafumi Sangai
  • Takeshi Nagashima
  • Masahiro Sakakibara
  • Nobumitsu Shiina
  • Masayuki Kuroda
  • Yasuyuki Aoyagi
  • Masaru Miyazaki
Preclinical study

Abstract

The objective of this study is to investigate interactions between adipocytes and breast cancer cells, and identify the responsible factors for the observed effects. In 27 breast cancer patients undergoing mastectomy, mammary adipose tissue was obtained from the breast quadrant bearing the tumor and corresponding non-tumoral quadrant. Isolated normal breast adipocytes (NBAs) and cancer-associated adipocytes (CAAs) were cultured in collagen gels to mimic the in vivo environment. Immunohistochemistry, qRT-PCR, and cell proliferation assays were performed to analyze adipocyte phenotypes. MCF7 and MDA-MB-231 breast cancer cell lines were co-cultured with adipocytes to detect phenotypic changes. Migration of MCF7 and MDA-MB-231 cells was assessed in NBA- and CAA-conditioned media. Cytokine levels in conditioned media were measured by cytokine array. Migration assays were repeated using conditioned media containing neutralizing antibodies. NBAs and CAAs lost their morphological phenotype in culture, acquiring a spindle-like shape, and CAAs showed higher cell proliferation, suggesting reversion to an immature phenotype. In co-cultures with MCF7 or MDA-MB-231 cells, NBAs exhibited increased cell proliferation, indicating acquisition of the immature phenotype of CAAs. MCF7 and MDA-MB-231 showed higher migration in a CAA-conditioned medium than in an NBA-conditioned medium. Cytokine array analysis of conditioned media revealed higher levels of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in the CAA-conditioned medium. Neutralization experiments using antibodies against IL-6 or MCP-1 showed abrogation of migration-enhancing effects of the CAA-conditioned medium. Adipocytes revert to an immature and proliferative phenotype in the presence of breast cancer cells, and promote cancer cell migration via adipokines including IL-6 and MCP-1.

Keywords

Breast cancer Adipocytes Cell migration Adipokines 

Supplementary material

10549_2015_3318_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 18 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Kaoru Fujisaki
    • 1
  • Hiroshi Fujimoto
    • 1
  • Takafumi Sangai
    • 1
  • Takeshi Nagashima
    • 1
  • Masahiro Sakakibara
    • 1
  • Nobumitsu Shiina
    • 1
  • Masayuki Kuroda
    • 2
  • Yasuyuki Aoyagi
    • 3
  • Masaru Miyazaki
    • 1
  1. 1.Department of General SurgeryChiba University Graduate School of MedicineChuo-KuJapan
  2. 2.Center for Advanced MedicineChiba University HospitalChuo-KuJapan
  3. 3.Clinical Cell Biology and MedicineChiba University Graduate School of MedicineChuo-KuJapan

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