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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-5-21
pubmed:abstractText
An invasion-independent pathway has been proposed as a novel mechanism in blood-borne metastasis, where tumour cells enveloped by sinusoidal tumour vessels enter the circulation without vascular invasion. We previously identified the secretory leukocyte protease inhibitor (SLPI) as a candidate gene responsible for this pathway. In this study, the functional role of SLPI in metastatic dissemination was investigated. We transfected the SLPI gene into a poorly metastatic clone of the MCH66 mouse mammary tumour cell line. Over-expression of SLPI promoted in vivo growth and spontaneous metastasis to the lung, whereas it suppressed invasive activity in vitro. The inoculated tumours of SLPI-transfectants exclusively induced a sinusoidal vasculature and subsequently produced endothelial-coated tumour emboli, which are morphological indices of the invasion-independent pathway. In addition, exogenous SLPI inhibited the migration activity through Matrigel of both tumour cells and human umbilical vein endothelial cells (HUVECs). In vivo angiogenesis assays also demonstrated that SLPI suppressed the migration of newly formed blood vessels. These results suggest that an anti-migratory effect of SLPI on tumour-associated endothelial cells may induce vascular remodelling to form a sinusoidal architecture, and consequently promote invasion-independent metastasis. This study provides a new model for metastasis, based on the mechanism regulated by anti-invasive factors, such as SLPI.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-3417
pubmed:author
pubmed:copyrightInfo
Copyright 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
212
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
152-60
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The secretory leukocyte protease inhibitor (SLPI) suppresses cancer cell invasion but promotes blood-borne metastasis via an invasion-independent pathway.
pubmed:affiliation
Department of Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan. sugino@fmu.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't