Regulation of cell growth and the expression of extracellular matrix proteins in colorectal adenocarcinoma: a fibroblast-tumor cell coculture model to study tumor-host interactions in vitro

Eur J Cell Biol. 2003 Jan;82(1):1-8. doi: 10.1078/0171-9335-00283.


The production of abundant connective tissue within malignant tumors, the so-called desmoplastic stromal reaction, is a hallmark of colorectal adenocarcinomas. This stroma is produced to a large extent by myofibroblasts and contains various amounts of collagens (type I, III, and V), chondroitin sulfate proteoglycan, hyaluronic acid, fibronectin, and tenascin-C. In this study we have established a monolayer coculture model between two different colorectal adenocarcinoma cell lines (HRT-18, and CX-2) and colonic fibroblasts (CCD-18) to investigate the mechanisms regulating (i) the production of extracellular matrix (ECM) components, (ii) the induction of myofibroblastic differentiation, and (iii) cellular proliferation. We found that TGFbeta1 and FGF-2 stimulated ECM synthesis of fibroblasts. Myofibroblastic differentiation was stimulated by TGFbeta1 but suppressed by FGF-2. There was a mutual stimulation of proliferation between fibroblasts and carcinoma cells. The analogies with ECM components expressed in cocultures and colorectal adenocarcinoma samples suggest that the coculture model used in this study is useful to study tumor cell-fibroblast interactions.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Cell Communication / drug effects
  • Cell Communication / physiology
  • Cell Culture Techniques / methods
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Coculture Techniques
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Connective Tissue / drug effects
  • Connective Tissue / metabolism*
  • Connective Tissue / ultrastructure
  • Extracellular Matrix Proteins / drug effects
  • Extracellular Matrix Proteins / metabolism*
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / ultrastructure
  • Humans
  • Inflammation Mediators / metabolism
  • Microscopy, Electron
  • Models, Biological
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Stromal Cells / ultrastructure
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1
  • Tumor Cells, Cultured


  • Extracellular Matrix Proteins
  • Inflammation Mediators
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Fibroblast Growth Factor 2