[Effect of hypoxia on production and secretion of matrix metalloproteinases in tumor cells].
OBJECTIVE
The malignant tumor tissues usually suffer from hypoxia due to its fast growth, which increases its invasive ability. This study was to explore changes of matrix metalloprotei-nases (MMPs) in tumor cells under hypoxia in vitro.


METHODS
Zymography was used to determine the changes of activities of MMP-2 and MMP-9 in pancreatic cancer cell line SW1990 cultured under hypoxia. Western blot, and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect protein and mRNA levels of MMP-2 and MMP-9.


RESULTS
Under normal circumstances, activities of MMPs in SW1990 cells were relatively low. When SW1990 cells were cultured under hypoxia, the activity of MMP-9 increased by about 5.5 times that in normal circumstances, while the activity of MMP-2 didn't change. The same changes in protein level of MMP-9 had been confirmed by Western blot, while protein level of MMP-2 didn't change. mRNA level of MMP-9 was higher in cells cultured under hypoxia for 12 h than in control cells and CoCl(2)-cultured tumor cells by 46.1% and 56.4%, but no change of MMP-9 was seen when hypoxia inducible factor-1alpha (HIF-1alpha) was produced in SW1990 cells stimulated by CoCl(2).


CONCLUSIONS
Production of MMP-9 in SW1990 cells is enhanced significantly under hypoxia, and its activity altered correspondingly; but those of MMP-2 had no change. This alteration has no relation with enhancement of HIF-1alpha under hypoxia.
Gao
Yong
Y
Department of Oncology, Changzheng Hospital, Shanghai, 200070, P. R. China. gaoyong@csco.org.cn
Wang
Jie-Jun
JJ
Wang
Ge-Fang
GF
Xu
Qing
Q
Guo
Jing
J
D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003035:Cobalt / Q000494:pharmacology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D003035:Cobalt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C018021:cobaltous chloride