In vitro dorsal root ganglia and human prostate cell line interaction: redefining perineural invasion in prostate cancer

Prostate. 2001 Nov 1;49(3):213-23. doi: 10.1002/pros.1137.


Background: Little is understood regarding mechanisms of perineural invasion in prostate cancer progression. We present a novel model system and data that indicate perineural invasion is an active, specific, and reciprocal interaction between nerves and prostate cancer cells.

Methods: Mouse dorsal root ganglia (DRG) and human prostate cancer cells (Du-145, LNCaP, PC3) and stromal cells (HTS-40F) were co-cultured in Matrigel matrix. Control cultures consisted of prostate cancer and stromal cells only and DRG only. Neurite outgrowth, cell colony growth, neurite-colony contact, and retrograde extension were quantitated with dark phase microscopy and image analysis (Optimas 6.1).

Results: Directional outgrowth of neurites was observed projecting into DU-145 colonies within 24 hr of co-culture. Cultures with the greatest number of DU-145 cells recruited significantly more neurites and established contact earlier, indicating this process was cell-seeding density dependent. Once neurite/DU-145 cell contact was established neurite growth diminished, suggesting an active neurite recruitment by DU-145 cells. Subsequent to neurite contact, DU-145 cells migrated along neurites in a retrograde fashion into the nerve/ganglion of origin (retrograde extension) establishing perineural invasion. In addition to perineural invasion, DU-145 colony growth was elevated in DRG co-cultures relative to DU-145-only control cell cultures. Similarly, the degree of neurite outgrowth was elevated in DRG-cell co-cultures relative to DRG-only control cultures. The same observations were made with LNCaP and PC3 cells, but interactions between stromal cells and nerves were not found.

Conclusions: This study shows the utility of the prostate cancer/DRG in vitro system to study specific mechanism of prostate cancer cell-nerve interaction. Moreover, these data suggest that perineural invasion mechanisms involve active and reciprocal interactions between carcinoma cells and adjacent nerve/ganglions in prostate cancer progression.

Publication types

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

MeSH terms

  • Animals
  • Biocompatible Materials
  • Cell Communication / physiology*
  • Coculture Techniques
  • Collagen
  • Drug Combinations
  • Ganglia, Spinal / pathology*
  • Humans
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Laminin
  • Male
  • Mice
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Neurites / pathology*
  • Prostate / innervation
  • Prostatic Neoplasms / pathology*
  • Proteoglycans
  • Stromal Cells
  • Tumor Cells, Cultured


  • Biocompatible Materials
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • matrigel
  • Collagen