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

C. A. Hart, M. Brown, Steven Bagley, H. Sharrard, N. W. Clarke

Research output: Contribution to journalArticlepeer-review


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 μM of the SDF-1 inhibitor T140. However, 10 μM 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. © 2005 Cancer Research UK.
Original languageEnglish
Pages (from-to)503-512
Number of pages9
JournalBritish Journal of Cancer
Issue number3
Publication statusPublished - 14 Feb 2005


  • Bone marrow
  • CXCR4
  • Endothelium
  • Metastasis
  • Prostate


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