Oxygen-Mediated Regulation of Gelatinase and Tissue Inhibitor of Metalloproteinases-1 Expression by Invasive Cells

Canning, Matthew T.; Postovit, Lynne-Marie; Clarke, Sarah H.; Graham, Charles H.

doi:10.1006/excr.2001.5243

Cited by 84 publications

(76 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At the cellular level, hypoxia induces changes that lead to cell survival, angiogenesis and invasion (Vaupel, 2004). Several studies have described the transcriptional upregulation of proteases and protease receptors, such as MMP-9 and urokinase-type plasminogen activator receptor (uPAR), as mechanisms involved in the hypoxia-induced cell invasion (Graham et al, 1999;Canning et al, 2001;Krishnamachary et al, 2003). However, we have identified the post-translational regulation of MT1-MMP as a novel mechanism for the hypoxia-induced invasion of breast carcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, many reports have linked hypoxia with the regulation of expression and/or activity of members of the MMP family, including MT1-MMP (Canning et al, 2001;Burke et al, 2003;Brat et al, 2004;Fahling et al, 2004;Ridgway et al, 2005). However, some of these reports are contradictory, and tumor-and cell type-specific constraints may exist.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hypoxia stimulates breast carcinoma cell invasion through MT1-MMP and MMP-2 activation

et al. 2005

View full text Add to dashboard Cite

The process of cancer cell invasion involves degradation of the extracellular matrix (ECM) by proteases, integrin adhesion and cell motility. The role of ECM degrading proteases on the hypoxia-induced invasion of breast carcinoma cells was investigated. Hypoxia markedly increased the invasion capacity of MDA-MB-231 and MDA-MB-435 breast carcinoma cell lines. Matrix metalloproteinase (MMP) inhibitors blocked the hypoxia-induced invasion, whereas other protease inhibitors had no effect. Antibodies or siRNAs blocking either membrane type-1 MMP (MT1-MMP) or MMP-2 were effective in reducing the hypoxia-induced invasion. Serumfree reconstitution experiments confirmed the involvement of the MT1-MMP/MMP-2/tissue inhibitor of metalloproteinase-2 complex in this hypoxia-induced response. Overexpression of MT1-MMP in a poorly invasive breast cancer cell line, T47-D, promoted hypoxia-induced invasion and MMP-2 activation. Cell surface accumulation and activation of MT1-MMP without apparent regulation at the mRNA or protein levels indicated a post-translational adaptive response to hypoxia. Inhibition of the small GTPase RhoA eliminated the hypoxiainduced invasion and blocked the localization of MT1-MMP to the plasma membrane. Zymographic and molecular analysis of human breast tumors showed a strong correlation between hypoxic microenvironments and MMP-2 activation without changes in MT1-MMP expression. Our studies suggest that hypoxic tumor microenvironments promote breast cancer invasion through an MT1-MMP-dependent mechanism.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypoxia stimulates breast carcinoma cell invasion through MT1-MMP and MMP-2 activation

et al. 2005

View full text Add to dashboard Cite

show abstract

“…16,[38][39][40] Our results indicated that in DU-145 cells MMP-9 and MMP2 levels did not change upon incubation in hypoxia or with the addition of GA to hypoxic-treated cells 18 used breast cancer cells to demonstrate in certain hypoxic cell lines in fact lead to increased MMP-9 but not MMP-2 levels. However, they kept their cells in hypoxia for 24 h. Other studies have demonstrated that VEGF can upregulate MMP-9 via its activation of VEGF receptors in different cell lines.…”

Section: Inhibition Of Hif-1a By Geldanamycinmentioning

confidence: 98%

“…They, however, did not see the same induction of MMP-9 in a poorly metastatic breast cancer cell line. 18 MMP-2 and MMP-9 expression were not changed under hypoxic conditions for a wide range of cell lines tested including prostate cancer cell lines. 19 These differences may be related to the malignant potential of various cell lines.…”

Section: Introductionmentioning

confidence: 96%

Effects of geldanamycin on HIF-1α mediated angiogenesis and invasion in prostate cancer cells

Alqawi

Moghaddas

Singh

2006

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

Geldanamycin (GA), a benzoquinone ansamycin, is a naturally occurring inhibitor of heat shock protein (Hsp90), which regulates the transcription activity of hypoxia-inducible factor 1 (HIF-1a). Under hypoxia, HIF-1a is activated in tumor cells, and induces the transcription of vascular endothelial growth factor (VEGF), which is the prime regulator for angiogenesis. VEGF promotes the formation of new blood vessels by stimulating endothelial cell division and migration. This eventually forms a vascular network that allows for tumor growth and metastasis. In this study, we used GA to inhibit HIF-1a transcription function. Human prostate cancer DU-145 cells were incubated in a hypoxic chamber at 1% O 2 and 371C for different durations. Both mRNA and protein levels of HIF-1a and VEGF were upregulated under hypoxic conditions. We demonstrated that GA treatment of hypoxic DU-145 cells abolished the induction of HIF-1a protein in a time-dependent manner and decreased VEGF mRNA and its protein levels. The transient transfection of DU-145 cells with luciferase reporter gene construct (5HRE/hCMVmp-luc) showed that the transcriptional activity of HIF-1a was significantly induced in response to hypoxia, but inhibited by GA. In addition, using conditioned medium from GA-treated hypoxic cells led to a significant decrease in cell invasion in comparison with using conditioned medium from nontreated hypoxic cells. These data provide evidence for the important role of GA in inhibition of angiogenesis and also invasion mediated by HIF-1a in prostate cancer cells.

show abstract

“…In several cancer cell lines, hypoxia and HGF were reported to synergize in inducing invasive growth [49]. One plausible explanation for these observations relies on the fact that the activity of proteases is promoted by hypoxia [51,52]. HGF needs to be extracellularly converted from its inactive precursor form, pro-HGF, to mature HGF by urokinase-type plasminogen activator in order to bind to MET.…”

Section: 2hif-related Transcriptional Activation Of Rtks: Met Axlmentioning

confidence: 99%

Interplay between receptor tyrosine kinases and hypoxia signaling in cancer

Glück

Aebersold

Zimmer

et al. 2015

The International Journal of Biochemistry & Cell Biology

View full text Add to dashboard Cite

Oxygen-Mediated Regulation of Gelatinase and Tissue Inhibitor of Metalloproteinases-1 Expression by Invasive Cells

Cited by 84 publications

References 37 publications

Hypoxia stimulates breast carcinoma cell invasion through MT1-MMP and MMP-2 activation

Hypoxia stimulates breast carcinoma cell invasion through MT1-MMP and MMP-2 activation

Effects of geldanamycin on HIF-1α mediated angiogenesis and invasion in prostate cancer cells

Interplay between receptor tyrosine kinases and hypoxia signaling in cancer

Contact Info

Product

Resources

About