Document Detail

Impact of hypoxia on the metastatic potential of human prostate cancer cells.
MedLine Citation:
PMID:  21640519     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Intratumoral hypoxia is known to be associated with radioresistance and metastasis. The present study examined the effect of acute and chronic hypoxia on the metastatic potential of prostate cancer PC-3, DU145, and LNCaP cells.
METHODS AND MATERIALS: Cell proliferation and clonogenicity were tested by MTT assay and colony formation assay, respectively. "Wound-healing" and Matrigel-based chamber assays were used to monitor cell motility and invasion. Hypoxia-inducible factor 1 alpha (HIF-1α) expression was tested by Western blot, and HIF-1-target gene expression was detected by real-time polymerase chain reaction. Secretion of matrix metalloproteinases (MMPs) was determined by gelatin zymography.
RESULTS: When PC-3 cells were exposed to 1% oxygen (hypoxia) for various periods of time, chronic hypoxia (≥24 h) decreased cell proliferation and induced cell death. In contrast, prostate cancer cells exposed to acute hypoxia (≤6 h) displayed increased motility, clonogenic survival, and invasive capacity. At the molecular level, both hypoxia and anoxia transiently stabilized HIF-1α. Exposure to hypoxia also induced the early expression of MMP-2, an invasiveness-related gene. Treatment with the HIF-1 inhibitor YC-1 attenuated the acute hypoxia-induced migration, invasion, and MMP-2 activity.
CONCLUSIONS: The length of oxygen deprivation strongly affected the functional behavior of all three prostate cancer cell lines. Acute hypoxia in particular was found to promote a more aggressive metastatic phenotype.
Yao Dai; Kyungmi Bae; Dietmar W Siemann
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-06-02
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  81     ISSN:  1879-355X     ISO Abbreviation:  Int. J. Radiat. Oncol. Biol. Phys.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-08-29     Completed Date:  2011-10-24     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  521-8     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
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MeSH Terms
Cell Death / physiology
Cell Hypoxia / physiology*
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation*
Cell Survival / physiology
Enzyme Inhibitors / pharmacology
Hypoxia-Inducible Factor 1 / antagonists & inhibitors,  metabolism
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Indazoles / pharmacology
Matrix Metalloproteinase 2 / genetics,  metabolism
Matrix Metalloproteinase 9 / genetics,  metabolism
Matrix Metalloproteinase Inhibitors
Neoplasm Invasiveness / genetics,  physiopathology,  prevention & control
Neoplasm Proteins / metabolism
Prostatic Neoplasms / metabolism,  pathology*,  physiopathology
Time Factors
Tumor Stem Cell Assay
Grant Support
R01 CA089655/CA/NCI NIH HHS; R01 CA089655/CA/NCI NIH HHS; R01 CA089655-01A1/CA/NCI NIH HHS
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Hypoxia-Inducible Factor 1; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Indazoles; 0/Matrix Metalloproteinase Inhibitors; 0/Neoplasm Proteins; 154453-18-6/3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; EC Metalloproteinase 2; EC Metalloproteinase 9

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

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