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PMID: 15668715 Published · ppublish English Journal Article

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

British journal of cancer ·Vol. 92 ·No. 3 ·2005-02-14 ·Pages 503-12

Hart CA, Brown M, Bagley S, Sharrard M, Clarke NW

Abstract

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
Chemicals
Oligopeptides Receptors, CXCR4 T140 peptide
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hart C A
PromPT Genito-Urinary Cancer Research, Cancer Research UK Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
Brown M
Bagley S
Sharrard M
Clarke N W
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
DOI
10.1038/sj.bjc.6602325
Published
2005-02-14
Pages
503-12
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2362089
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjc.6602325 PMC Full Text View journal details
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