title: Studies of type IV collagenase regulation by hypoxia.
abstract: Recent data suggest that patients with more hypoxic solid tumors are more likely to develop metastases and die. We speculated that upregulation of the metastasis-associated type IV collagenase MMP-9 (gelatinase B) by hypoxia might be correlated with the increased risk of distant failure in patients with hypoxic tumors. The promoter for MMP-9 contains consensus binding sites for the transcription factors NFkappaB and AP-1 which are upregulated under hypoxic conditions in HeLa cells and these transcription factors are critical to transcriptional activation of the MMP-9 gene. A variety of tumor cell lines were examined for induction of MMP-9 and the related protease MMP-2 under hypoxic conditions. Although hypoxia did upregulate MMP-9 in one alveolar rhabdomyosarcoma cell line, we were unable to demonstrate a consistent hypoxia-mediated increase in MMP-9 protein, RNA, or transcriptional activity measured with reporter constructs. These results suggest that MMP-9 expression is not directly affected by exposure to hypoxia in vitro.
authors.affiliation: Department of Pediatrics, University of Pennsylvania School of Medicine, The Children's Hospital of Philadelphia, 19104, USA. Himelstein@kermit.oncol.chop.edu
authors.forename: B P
authors.initials: BP
authors.lastname: Himelstein
authors.forename: C J
authors.initials: CJ
authors.lastname: Koch
mesh_terms: D015152:Blotting, Northern; D015687:Cell Hypoxia; D017364:Collagenases / Q000096:biosynthesis*; D016895:Culture Media, Serum-Free; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020780:Matrix Metalloproteinase 9; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D016895:Culture Media, Serum-Free; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D010100:Oxygen