STUDIES OF TYPE-IV COLLAGENASE REGULATION BY HYPOXIA

Recent data suggest that patients with more hypoxic solid tumors are m ore likely to develop metastases and die. We speculated that upregulat ion of the metastasis-associated type TV 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 contai ns consensus binding sites for the transcription factors NFKB and AP-I which are upregulated under hypoxic conditions in HeLa cells and thes e transcription factors are critical to transcriptional activation of the MMP-9 gene. A variety of tumor cell lines were examined for induct ion 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-mediate d 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. Published b y Elsevier Science Ireland Ltd.