Matrix metalloproteinases in tumor invasion

Johansson, Nina; Ahonen, Matti; Kähäri, Veli‐Matti

doi:10.1007/s000180050495

Cited by 292 publications

(210 citation statements)

References 92 publications

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“…Among STEAP1-regulated genes, we focused on MMP-1, ADIPOR1, and DTX3L all of which are implicated in ROS signaling. For instance, MMP-1 has been shown to be highly ROS inducible (34,46) and its overexpression increases invasiveness and metastasis of a variety of cancers (47). ADIPOR1 is the cognate receptor for adiponectin, which stimulates proliferation of hematopoietic stem cells (48).…”

Section: Discussionmentioning

confidence: 99%

STEAP1 Is Associated with the Invasive and Oxidative Stress Phenotype of Ewing Tumors

Grünewald

Diebold

Espósito

et al. 2012

Molecular Cancer Research

114

132

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Ewing tumors comprise the second most common type of bone-associated cancer in children and are characterized by oncogenic EWS/FLI1 fusion proteins and early metastasis. Compelling evidence suggests that elevated levels of intracellular oxidative stress contribute to enhanced aggressiveness of numerous cancers, possibly including Ewing tumors. Using comprehensive microarray analyses and RNA interference, we identified the six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-a membrane-bound mesenchymal stem cell marker of unknown function-as a highly expressed protein in Ewing tumors compared with benign tissues and show its regulation by EWS/FLI1. In addition, we show that STEAP1 knockdown reduces Ewing tumor proliferation, anchorage-independent colony formation as well as invasion in vitro and decreases growth and metastasis of Ewing tumor xenografts in vivo. Moreover, transcriptome and proteome analyses as well as functional studies revealed that STEAP1 expression correlates with oxidative stress responses and elevated levels of reactive oxygen species that in turn are able to regulate redox-sensitive and proinvasive genes. In synopsis, our data suggest that STEAP1 is associated with the invasive behavior and oxidative stress phenotype of Ewing tumors and point to a hitherto unanticipated oncogenic function of STEAP1. Mol Cancer Res; 10(1); 52-65. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

STEAP1 Is Associated with the Invasive and Oxidative Stress Phenotype of Ewing Tumors

Grünewald

Diebold

Espósito

et al. 2012

Molecular Cancer Research

114

132

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“…In addition, the tumor cells used in our studies express a protease(s) that cleaves FasL, as shown by the release of sFasL into the supernatant of in vitro, propagated tumor cells. Many laboratories have shown that MMPs are overexpressed in cancers and play an important role in cancer invasion and metastases (25)(26)(27). In particular, MMP7 is upregulated in endometrial, gastric, and colorectal cancers, and the MMP7 activity correlates with vascular invasion and metastases (28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

Control of Ocular Tumor Growth and Metastatic Spread by Soluble and Membrane Fas Ligand

et al. 2007

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Fas ligand (FasL) can be either membrane bound, or cleaved by metalloproteinases (MMP) to produce a soluble protein.The two different forms of FasL are reported to have opposite functions-membrane-bound FasL (mFasL) is proinflammatory and soluble FasL (sFasL) is antiinflammatory. We previously showed that, within the immune-privileged eye, tumors expressing high levels of mFasL overcame the suppressive ocular environment, triggered an inflammatory response, and were subsequently rejected. By contrast, eye tumors expressing low levels of mFasL grew progressively. To evaluate the effect of sFasL on the tumor growth and metastatic potential of ocular FasL-expressing tumors, we compared tumor cell clones that expressed equal amounts of (low) mFasL in the presence or absence of sFasL. Tumor cells transfected with a modified FasL gene expressed only mFasL (noncleavable), grew progressively within the eye, and induced systemic protective immunity that prevented metastatic spread of tumor cells to the liver. Unexpectedly, tumors transfected with wild-type FasL (wtFasL; cleavable), which could produce both sFasL and mFasL, elicited considerably more inflammation and grew more slowly within the eye. However, the cleavable wtFasL eye tumors failed to trigger protective immunity and gave rise to liver metastases. Interestingly, exposure to the ocular environment was required for the wtFasL tumors to gain metastatic potential. We conclude that the fate of FasL-expressing tumors is determined by a combination of the following: (a) the relative proportion of membrane and sFasL, and (b) the local environment that determines the extent of FasL cleavage.

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“…MMPs, which are mainly produced by nonmalignant stromal cells, may be involved because these enzymes constitute a mechanism of tumor growth, invasion, and metastasis. 97 Tissue inhibitors of MMPs have been suggested to be useful in combination therapy with TRAIL because an MMP-2/ MMP-9 inhibitor caused reduced tumor growth and angiogenesis in nude mice. 98 However, the role of tissue inhibitors of MMPs in combination with TRAIL needs to be further investigated to determine the extent to which these molecules can overcome microenvironmentally induced resistance to TRAIL.…”

Section: Influence Of the Tumor Microenvironment On Trail-induced Apomentioning

confidence: 99%

On the TRAIL to therapeutic intervention in liver disease

2007

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Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide. The fact that HCC is resistant to conventional chemotherapy and is rarely amenable to radiotherapy leaves this disease with no effective therapeutic options and a very poor prognosis. Therefore, the development of more effective therapeutic tools and strategies is much needed. HCCs are phenotypically and genetically heterogeneous tumors that commonly emerge on a background of chronic liver diseases, most of which culminate in cirrhosis, such as alcoholic cirrhosis and chronic hepatitis B and C infections. This review outlines recent findings on the progression of liver disease, including our knowledge of the role of apoptotic processes, with an emphasis on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The proapoptotic and antiapoptotic properties of TRAIL, its involvement in liver injury, and its potential as a therapeutic agent in fibrosis and HCC are discussed. Several contradictory and confusing data have not yet been resolved or placed into perspective, such as the influence of factors that determine the TRAIL sensitivity of target cells, including the tumor microenvironment or cirrhotic tissue. Therefore, we assess these data from the perspectives of gastroenterologists (P.S. and M.W.B.) and a molecular oncologist (I.H.) with research interests in liver injury, apoptosis, and experimental therapeutics. (HEPATOLOGY

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Matrix metalloproteinases in tumor invasion

Cited by 292 publications

References 92 publications

STEAP1 Is Associated with the Invasive and Oxidative Stress Phenotype of Ewing Tumors

STEAP1 Is Associated with the Invasive and Oxidative Stress Phenotype of Ewing Tumors

Control of Ocular Tumor Growth and Metastatic Spread by Soluble and Membrane Fas Ligand

On the TRAIL to therapeutic intervention in liver disease

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