Document Detail


pH, hypoxia and metastasis.
MedLine Citation:
PMID:  11727927     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The vascular supply to tumours is often poorly formed and irregular with the result that tumours may contain regions of poor nutritional supply with hypoxia and acidic pH. Clinical studies have demonstrated substantial heterogeneity in oxygenation in human tumours. In some studies tumours with poorer oxygenation were more likely to have metastasized. In our studies of carcinoma of the cervix, nodal metastases were 1.5 times more likely at diagnosis in patients with more hypoxic tumours relative to those with less hypoxic tumours. Transplanted rodent KHT fibrosarcomas and SCC-VII squamous cell tumours also have variability in levels of oxygenation; again, the more hypoxic tumours are found to be more metastatic. Furthermore, deliberate exposure of KHT tumours to cyclic hypoxia (12 cycles of 5% oxygen breathing for 10 min interspersed with 10 min air breathing) every day during their growth, doubled the level of micrometastases that were detected in the lungs of the mice. These findings are consistent with in vitro studies demonstrating that KHT and SCC-VII cells and B-16 melanoma cells exposed to hypoxia or low pH have increased propensity to form metastases following injection into-mice. This effect is transient and is lost within about 48 h of removal of exposure to hypoxia or low pH, suggesting that the effect may be due to changes in gene expression associated with that stress. Recent studies have implicated a number of genes, such as vascular endothelial growth factor and interleukin 8, in the effect of hypoxic and acid pH on metastasis.
Authors:
R P Hill; K De Jaeger; A Jang; R Cairns
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Novartis Foundation symposium     Volume:  240     ISSN:  1528-2511     ISO Abbreviation:  Novartis Found. Symp.     Publication Date:  2001  
Date Detail:
Created Date:  2001-11-30     Completed Date:  2002-05-09     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  9807767     Medline TA:  Novartis Found Symp     Country:  England    
Other Details:
Languages:  eng     Pagination:  154-65; discussion 165-8     Citation Subset:  IM    
Affiliation:
Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, Canada.
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MeSH Terms
Descriptor/Qualifier:
Aerobiosis
Cell Hypoxia*
Extracellular Space / physiology
Humans
Hydrogen-Ion Concentration*
Neoplasm Metastasis*
Neoplasms / metabolism,  pathology
Prognosis

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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