Document Detail


Elevated cell invasion is induced by hypoxia in a human pituitary adenoma cell line.
MedLine Citation:
PMID:  19262092     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pituitary adenoma tissues are hypovascular, and have a lower partial oxygen pressure compared with neighboring normal organs. In this study, we investigated whether hypoxia influences the cell invasiveness of the human pituitary adenoma cell line, HP-75. HP-75 cells were exposed to hypoxic (1-10% oxygen) or normoxic (21% oxygen) conditions for 24 hours. Gelatin and reverse zymogram assays were used to determine the enzyme activities of matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP). Cell adhesion and Matrigel cell invasion were examined with a Boiden chamber. Finally, the mRNA gene expression profiles of cells exposed to hypoxia or normoxia were examined by cDNA microarray and confirmed with real-time RT-PCR and flow cytometry. The gelatin and reverse zymograms revealed that the activities of MMP and TIMP were not significantly altered by hypoxia. Matrigel cell invasion and cell adhesion to Matrigel or collagen type IV were increased by hypoxia (3.8- and 4.8-fold, respectively). The cDNA microarray analysis revealed that laminin beta2 chain mRNA was specifically up-regulated under hypoxic conditions (4.96-fold). Finally, real-time RT-PCR and flow cytometry verified the elevated expression of laminin beta2 chain at the mRNA and protein levels under hypoxic conditions. RNA interference with siRNA targeting laminin beta2 inhibited Matrigel invasion and adhesion to collagen type IV in a dose-dependent manner. Collectively, these results suggested that hypoxia (1% oxygen) enhanced the cell invasion properties of a pituitary adenoma cell line in association with elevated expression of laminin beta2 and enhanced binding to collagen type IV.
Authors:
Daizo Yoshida; Akira Teramoto
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-27
Journal Detail:
Title:  Cell adhesion & migration     Volume:  1     ISSN:  1933-6926     ISO Abbreviation:  Cell Adh Migr     Publication Date:    2007 Jan-Mar
Date Detail:
Created Date:  2009-03-05     Completed Date:  2009-06-04     Revised Date:  2010-12-07    
Medline Journal Info:
Nlm Unique ID:  101469464     Medline TA:  Cell Adh Migr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  43-51     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, Nippon Medical School, Nippon Medical School, Tokyo, Japan. dyoshida@nms.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adenoma / genetics,  metabolism*,  pathology
Cell Hypoxia / genetics
Cell Line, Tumor
Collagen Type IV / biosynthesis,  genetics
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Humans
Laminin / biosynthesis,  genetics
Matrix Metalloproteinases / biosynthesis,  genetics
Neoplasm Invasiveness
Neoplasm Proteins / biosynthesis*,  genetics
Oligonucleotide Array Sequence Analysis
Oxygen / metabolism*
Pituitary Neoplasms / genetics,  metabolism*,  pathology
RNA, Messenger / biosynthesis,  genetics
RNA, Neoplasm / biosynthesis,  genetics
RNA, Small Interfering / genetics
Tissue Inhibitor of Metalloproteinases / biosynthesis,  genetics
Chemical
Reg. No./Substance:
0/Collagen Type IV; 0/Laminin; 0/Neoplasm Proteins; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/RNA, Small Interfering; 0/Tissue Inhibitor of Metalloproteinases; 124148-86-3/laminin beta2; 7782-44-7/Oxygen; EC 3.4.24.-/Matrix Metalloproteinases
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