Epithelial to mesenchymal transition in human breast cancer can provide a nonmalignant stroma

Am J Pathol. 2003 Feb;162(2):391-402. doi: 10.1016/S0002-9440(10)63834-5.


A breast carcinoma biopsy showed cytochemical evidence of epithelial mesenchymal transition and an alpha-smooth muscle actin-positive stromal reaction. To study the lineage, and the nature of the cells in the stromal reaction, we derived a novel cell line, HBFL-1, from the explanted biopsy. HBFL-1 cells are immortal and exhibit a shared non-random X-chromosome inactivation pattern with the epithelial tumor of origin. Yet they closely resemble normal, finite-life-span fibroblasts by morphology, lack of tumor formation in nude mice, marker expression profile, protein pattern using two-dimensional gel electrophoresis and the ability to undergo myofibroblast conversion. HBFL-1 interacts reciprocally with tumor cells in collagen gel to induce activation of MMP2, leading to tumor-like behavior of epithelial colonies. In vivo, HBFL-1 cells resembled normal-derived myofibroblasts and conferred a significant 3.5- to 7-fold increase in MCF-7 tumor size in nude mice. However, that they were indeed not normal fibroblasts was revealed by residual keratin expression and formation of epithelial microfoci in a reconstituted basement membrane and in nude mice. We conclude that breast cancer can generate its own nonmalignant stroma and that one function for this is that of a reciprocal interaction with epithelial tumor cells to facilitate tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Basement Membrane / pathology
  • Biomarkers, Tumor / analysis
  • Biopsy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Culture Techniques / methods
  • Cell Transformation, Neoplastic*
  • Chromosomes, Human, X
  • Cytokines / pharmacology
  • Enzyme Activation
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Karyotyping
  • Matrix Metalloproteinase 2 / metabolism
  • Mesoderm / pathology
  • Receptors, Androgen / analysis
  • Stromal Cells / cytology*
  • Tumor Cells, Cultured


  • Biomarkers, Tumor
  • Cytokines
  • Receptors, Androgen
  • Matrix Metalloproteinase 2