Enhanced in vitro invasiveness of ovarian cancer cells through up-regulation of VEGF and induction of MMP-2

Zhang, Ali; Li, Meng; Wang, Qunsheng; Xi, Ling; Chen, Gang; Wang, Shixuan; Zhou, Jianfeng; Lu, Yao; Ma, Ding

doi:10.3892/or.15.4.831

Cited by 32 publications

(35 citation statements)

References 20 publications

(23 reference statements)

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“…Both HIF1 and 2 were shown to regulate hypoxic MDM induction of VEGFA, GLUT-1, CXCR4, IL-1 , IL-8, and ADM (Fang et al, 2009) (Figure 1b), validating other reports of these as HIF target genes (Benita et al, 2009;Hirani et al, 2001;Semenza, 2003;Zhang et al, 2006).…”

Section: Transcription Factors Hifs 1 Andsupporting

confidence: 74%

“…Various experimental methods have been used to identify HIF targets, including loss of expression in HIF-null cells (Fang et al, 2009;Semenza, 2003), targeting transcribed HIF using siRNA treatment (Fang et al, 2009;Kamlah et al, 2009;Krishnamachary et al, 2003), overexpression of HIFs using expression vectors or induced gene expression in von HippelLindau (VHL)-null cells (Wykoff et al, 2000), or by the identification of HREs and HIF binding sites within gene promoter regions (Benita et al, 2009;Hirani et al, 2001;Semenza and Wang, 1992;Zhang et al, 2006). Both HIF1 and 2 were shown to regulate hypoxic MDM induction of VEGFA, GLUT-1, CXCR4, IL-1 , IL-8, and ADM (Fang et al, 2009) (Figure 1b), validating other reports of these as HIF target genes (Benita et al, 2009;Hirani et al, 2001;Semenza, 2003;Zhang et al, 2006).…”

Section: Transcription Factors Hifs 1 Andmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Hypoxia in Re-educating Macrophages in the Tumour Environment

Harwood¹,

Lewis²,

Biswas³

2012

Tumor Microenvironment and Myelomonocytic Cells

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Section: Transcription Factors Hifs 1 Andsupporting

confidence: 74%

Section: Transcription Factors Hifs 1 Andmentioning

confidence: 99%

The Role of Hypoxia in Re-educating Macrophages in the Tumour Environment

Harwood¹,

Lewis²,

Biswas³

2012

Tumor Microenvironment and Myelomonocytic Cells

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“…Recently, cross-talk between VEGF and MMP-9 has been suggested to play a role in ovarian carcinoma invasion and metastasis. [37][38][39][40] Host cells, specifically inflammatory cells as opposed to tumor cells, have been implicated as being the primary source of MMP-9 in these models. 37 Previous studies have determined that VEGF-mediated inflammation plays a critical role in the pathological angiogenesis induced by it.…”

Section: Discussionmentioning

confidence: 99%

Cross-Talk between Vascular Endothelial Growth Factor and Matrix Metalloproteinases in the Induction of Neovascularization in Vivo

Ebrahem

Chaurasia

Vasanji

et al. 2010

The American Journal of Pathology

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Matrix metalloproteinases (MMPs), a specialized group of enzymes capable of proteolytically degrading extracellular matrix proteins , have been postulated to play an important role in angiogenesis. It has been suggested that MMPs can regulate neovascularization using mechanisms other than simple remodeling of the capillary basement membrane. To determine the interplay between vascular endothelial growth factor (VEGF) and MMPs , we investigated the induction of angiogenesis by recombinant active MMPs and VEGF in vivo. Using a rat corneal micropocket in vivo angiogenesis assay , we observed that the active form of MMP-9 could induce neovascularization in vivo when compared with the pro-form of the enzyme as a control. This angiogenic response could be inhibited by neutralizing VEGF antibody , which suggests that MMPs acts upstream of VEGF. Additional in vitro studies using extracellular matrix loaded with radiolabeled VEGF determined that active MMPs can enzymatically release sequestered VEGF. Interestingly, in vivo angiogenesis induced by VEGF could be inhibited by MMP inhibitors , indicating that MMPs also act downstream of VEGF. In addition , inflammation plays an important role in the induction of angiogenesis mediated by both VEGF and MMPs. Our results suggest that MMPs act both upstream and downstream of VEGF and imply that potential combination therapies of VEGF and MMP inhibitors may be a useful therapeutic approach in diseases of pathological neovascularization.

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“…By virtue of their activity, MMPs are most closely associated with the invasive and metastatic aspect of cancer progression, as increased MMP activity allows cancer cells to invade through the ECM and metastasize into other tissues (Zhang et al 2006). MMPs are overexpressed in almost all human cancers and high MMP expression usually correlates with a poor prognosis (Rhee and Coussens 2002).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the MMP-dependent and independent functions of tissue inhibitor of metalloproteinase-2 on the invasiveness of breast cancer cells

Walsh

Cepeda

Damjanovski

2012

J. Cell Commun. Signal.

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Matrix metalloproteinases (MMPs) are secreted endopeptidases that play an essential role in remodeling the extracellular matrix (ECM). MMPs are primarily active during development, when the majority of ECM remodeling events occurs. In adults, elevated MMP activity has been observed in many pathological conditions such as cancer and osteoarthritis. The proteolytic activity of MMPs is controlled by their natural inhibitors -the tissue inhibitor of metalloproteinases (TIMPs). In addition to blocking MMPmediated proteolysis, TIMPs have a number of MMPindependent functions including binding to cell surface proteins thereby stimulating signaling cascades. TIMP-2, the most studied member of the family, can both inhibit and activate MMPs directly, as well as inhibit MMP activity indirectly by upregulating expression of RECK, a membrane anchored MMP regulator. While TIMP-2 has been shown to play important roles in breast cancer, we describe how the MMP-independent effects of TIMP-2 can modulate the invasiveness of MCF-7, T47D and MDA-MB-231 breast cancer cells. Using an ALA + TIMP-2 mutant which is devoid of MMP inhibition, but still capable of initiating specific cell signaling cascades, we show that TIMP-2 can differentially affect MMP activity and cellular invasiveness in both an MMP dependent and independent manner. More specifically, MMP activity and invasiveness is increased with the addition of exogenous TIMP-2 in poorly invasive cell lines whereas it is decreased in highly invasive cells lines (MDA-MB-231). Conversely, the addition of ALA + TIMP-2 resulted in decreased invasiveness regardless of cell line.

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Enhanced in vitro invasiveness of ovarian cancer cells through up-regulation of VEGF and induction of MMP-2

Cited by 32 publications

References 20 publications

The Role of Hypoxia in Re-educating Macrophages in the Tumour Environment

The Role of Hypoxia in Re-educating Macrophages in the Tumour Environment

Cross-Talk between Vascular Endothelial Growth Factor and Matrix Metalloproteinases in the Induction of Neovascularization in Vivo

Analysis of the MMP-dependent and independent functions of tissue inhibitor of metalloproteinase-2 on the invasiveness of breast cancer cells

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