Invasive characteristics of human prostatic epithelial cells: understanding the metastatic process

Br J Cancer. 2005 Feb 14;92(3):503-12. doi: 10.1038/sj.bjc.6602325.


Prostate cancer has a predilection to metastasise to the bone marrow stroma (BMS) by an as yet uncharacterised mechanism. We have defined a series of coculture models of invasion, which simulate the blood/BMS boundary and allow the elucidation of the signalling and mechanics of trans-endothelial migration within the complex bone marrow environment. Confocal microscopy shows that prostate epithelial cells bind specifically to bone marrow endothelial-to-endothelial cell junctions and initiate endothelial cell retraction. Trans-endothelial migration proceeds via an epithelial cell pseudopodial process, with complete epithelial migration occurring after 232+/-43 min. Stromal-derived factor-1 (SDF-1)/CXCR4 signalling induced PC-3 to invade across a basement membrane although the level of invasion was 3.5-fold less than invasion towards BMS (P=0.0007) or bone marrow endothelial cells (P=0.004). Maximal SDF-1 signalling of invasion was completely inhibited by 10 microM of the SDF-1 inhibitor T140. However, 10 microM T140 only reduced invasion towards BMS and bone marrow endothelial cells by 59% (P=0.001) and 29% (P=0.011), respectively. This study highlights the need to examine the potential roles of signalling molecules and/or inhibitors, not just in single-cell models but in coculture models that mimic the complex environment of the bone marrow.

MeSH terms

  • Bone Marrow Cells / physiology*
  • Cell Communication
  • Cell Movement
  • Coculture Techniques
  • Endothelium / physiology
  • Epithelial Cells / physiology
  • Female
  • Humans
  • Intercellular Junctions / physiology
  • Male
  • Microscopy, Confocal
  • Models, Biological
  • Neoplasm Metastasis*
  • Oligopeptides / pharmacology
  • Prostate / cytology
  • Prostatic Neoplasms / pathology*
  • Receptors, CXCR4 / physiology
  • Signal Transduction
  • Stromal Cells / physiology
  • Tumor Cells, Cultured


  • Oligopeptides
  • Receptors, CXCR4
  • T140 peptide