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

2.50
Hdl Handle:
http://hdl.handle.net/10541/76853
Title:
Invasive characteristics of human prostatic epithelial cells: understanding the metastatic process.
Authors:
Hart, Claire A; Brown, Michael D; Bagley, Steven; Sharrard, M; Clarke, Noel W ( 0000-0001-7776-8059 )
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.
Affiliation:
PromPT Genito-Urinary Cancer Research, Cancer Research UK Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
Citation:
Invasive characteristics of human prostatic epithelial cells: understanding the metastatic process. 2005, 92 (3):503-12 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
14-Feb-2005
URI:
http://hdl.handle.net/10541/76853
DOI:
10.1038/sj.bjc.6602325
PubMed ID:
15668715
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHart, Claire A-
dc.contributor.authorBrown, Michael D-
dc.contributor.authorBagley, Steven-
dc.contributor.authorSharrard, M-
dc.contributor.authorClarke, Noel W-
dc.date.accessioned2009-08-10T17:20:25Z-
dc.date.available2009-08-10T17:20:25Z-
dc.date.issued2005-02-14-
dc.identifier.citationInvasive characteristics of human prostatic epithelial cells: understanding the metastatic process. 2005, 92 (3):503-12 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid15668715-
dc.identifier.doi10.1038/sj.bjc.6602325-
dc.identifier.urihttp://hdl.handle.net/10541/76853-
dc.description.abstractProstate 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.en
dc.language.isoenen
dc.subjectCancer Metastasisen
dc.subjectProstatic Canceren
dc.subjectCultured Tumour Cellsen
dc.subject.meshBone Marrow Cells-
dc.subject.meshCell Communication-
dc.subject.meshCell Movement-
dc.subject.meshCoculture Techniques-
dc.subject.meshEndothelium-
dc.subject.meshEpithelial Cells-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshIntercellular Junctions-
dc.subject.meshMale-
dc.subject.meshMicroscopy, Confocal-
dc.subject.meshModels, Biological-
dc.subject.meshNeoplasm Metastasis-
dc.subject.meshOligopeptides-
dc.subject.meshProstate-
dc.subject.meshProstatic Neoplasms-
dc.subject.meshReceptors, CXCR4-
dc.subject.meshSignal Transduction-
dc.subject.meshStromal Cells-
dc.subject.meshTumor Cells, Cultured-
dc.titleInvasive characteristics of human prostatic epithelial cells: understanding the metastatic process.en
dc.typeArticleen
dc.contributor.departmentPromPT Genito-Urinary Cancer Research, Cancer Research UK Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.en
dc.identifier.journalBritish Journal of Canceren

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