Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer

Cancer Res. 2013 Sep 15;73(18):5657-68. doi: 10.1158/0008-5472.CAN-13-0530. Epub 2013 Jul 31.


Cancer-associated fibroblasts (CAF) comprise the majority of stromal cells in breast cancers, yet their precise origins and relative functional contributions to malignant progression remain uncertain. Local invasion leads to the proximity of cancer cells and adipocytes, which respond by phenotypical changes to generate fibroblast-like cells termed as adipocyte-derived fibroblasts (ADF) here. These cells exhibit enhanced secretion of fibronectin and collagen I, increased migratory/invasive abilities, and increased expression of the CAF marker FSP-1 but not α-SMA. Generation of the ADF phenotype depends on reactivation of the Wnt/β-catenin pathway in response to Wnt3a secreted by tumor cells. Tumor cells cocultivated with ADFs in two-dimensional or spheroid culture display increased invasive capabilities. In clinical specimens of breast cancer, we confirmed the presence of this new stromal subpopulation. By defining a new stromal cell population, our results offer new opportunities for stroma-targeted therapies in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology*
  • Animals
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Fluorescent Antibody Technique
  • Humans
  • Immunoenzyme Techniques
  • Mice
  • Mice, Nude
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • S100 Calcium-Binding Protein A4
  • S100 Proteins / genetics
  • S100 Proteins / metabolism
  • Spheroids, Cellular / pathology*
  • Stromal Cells / metabolism
  • Stromal Cells / pathology*
  • Tumor Microenvironment*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • Fibronectins
  • RNA, Messenger
  • S100 Calcium-Binding Protein A4
  • S100 Proteins
  • S100a4 protein, mouse
  • Wnt Proteins
  • beta Catenin