The plasminogen-plasmin system in malignancy

Kwaan, Hau C.

doi:10.1007/bf01307184

Cited by 178 publications

(109 citation statements)

References 221 publications

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“…A previous study of recombinant TFPI-2 showed that TFPI-2 inhibited the generation of plasmin at the surfaces of ECM and HT-1080 ®brosarcoma cells and inhibited the degradation and invasion of matrix by these cells (Rao et al, 1998). TFPI-2 directly inhibits plasmin, thereby releasing growth factors from ECM and activating transforming growth factor b and certain pro-MMPs by tumor cells, which causes degradation of ECM followed by invasion (Kwaan, 1992;Rao et al, 1999). One of the possible reasons might be that over expression of TFPI-2 is blocking the plasmin activation, therefore ECM is not destructed even though high levels of uPA, tPA and thrombin are present.…”

Section: Discussionmentioning

confidence: 99%

“…Expressed amounts of urokinase-type plasminogen activator (uPA) and uPA receptors (uPAR) in particular correlate directly with the invasiveness of human gliomas (Yamamoto et al, 1994;Gladson et al, 1995). Receptor-bound uPA converts the zymogen plasminogen to plasmin, a broad-spectrum serine protease that promotes lysis and dissolution of the extracellular matrix (ECM) and promotes tumor cell invasion (Mignatti and Rifkin, 1993;Murphy et al, 1992;Vassalli et al, 1985;Kwaan, 1992;Kramer et al, 1994). Inhibitors of plasmin probably play a role in the regulation of the invasive and malignant behavior of gliomas.…”

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confidence: 99%

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A novel function of tissue factor pathway inhibitor-2 (TFPI-2) in human glioma invasion

Konduri

Rao²,

Chandrasekar

et al. 2001

Oncogene

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Human tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine protease inhibitor that inhibits plasmin, trypsin, chymotrypsin, cathepsin G, and plasma kallikrein but not urokinase-type plasminogen activator, tissue plasminogen activator, or thrombin. Preliminary ®ndings in our laboratory suggested that the expression of TFPI-2 is downregulated or lost during tumor progression in human gliomas. To investigate the role of TFPI-2 in the invasiveness of brain tumors, we stably transfected the human high-grade glioma cell line SNB19 and the human low-grade glioma cell line Hs683 with a vector capable of expressing a transcript complementary to the full-length TFPI-2 mRNA in either sense (0.7 kb) or antisense (1 kb) orientations. Parental cells and stably transfected cell lines were analysed for TFPI-2 protein by Western blotting and for TFPI-2 mRNA by Northern blotting. The levels of TFPI-2 protein and mRNA were higher in the sense clones (SNB19) and decreased in the antisense (Hs683) clones than in the corresponding parental and vector controls. In spheroid and matrigel invasion assays, the SNB19 parental cells were highly invasive, but the sense-transfected SNB-19 clones were much less invasive; the antisense-transfected Hs683 clones were more invasive than their parental and vector controls. After intracerebral injection in mice, the sensetransfected SNB19 clones were less able to form tumors than were their parental and vector controls, and the antisense-Hs683 clones but not the parental or vector controls formed small tumors. This is the ®rst study to demonstrate that down-or upregulation of TFPI-2 plays a signi®cant role in the invasive behavior of human gliomas. Oncogene (2001) 20, 6938 ± 6945.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A novel function of tissue factor pathway inhibitor-2 (TFPI-2) in human glioma invasion

Konduri

Rao²,

Chandrasekar

et al. 2001

Oncogene

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“…Inactivation of Plasmin by Pseudocathepsin D-Plasmin is known to play a key role in producing angiogenic factors such as MMPs and cytokines (22). Cancer invasion is thought to be initiated by the activation of plasminogen and procollagenase cascade (23,24).…”

Section: Generation Of Angiostatic Peptides By Cathepsin E and Pepsinmentioning

confidence: 99%

“…Cancer invasion is thought to be initiated by the activation of plasminogen and procollagenase cascade (23,24). In addition, plasmin has been shown to be important in cancer-mediated conversion of plasminogen to angiostatin (14,22,25). These results thus suggest that inactivation of plasmin modulates angiogenesis in tumors.…”

Section: Generation Of Angiostatic Peptides By Cathepsin E and Pepsinmentioning

confidence: 99%

Angiostatin Generation by Cathepsin D Secreted by Human Prostate Carcinoma Cells

Morikawa¹,

Yamamoto²,

Ishikawa³

et al. 2000

Journal of Biological Chemistry

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“…PAs cleave plasminogen to the active proteinase plasmin, which can catalyse the degradation of a variety of proteins including fibrin and laminin (Kwaan, 1992), as well as activating other proteinases by cleaving the pro-form, e.g. MMP-1 (interstitial collagenase).…”

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confidence: 99%

Proteolysis in human breast and colorectal cancer

1999

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Summary Proteolysis occurs when proteinase activity exceeds inhibitor activity. Proteolysis is normally tightly regulated and is involved in cancer invasion and metastasis. The aim of this study was to compare proteolysis in breast and colorectal cancer. Proteinase and inhibitor expression were analysed in paired tumour and normal tissue samples from 43 breast and 24 colorectal cancer patients using substrate zymography, Western blotting and quenched fluorescence substrate hydrolysis. The expression of the latent forms of matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9, urokinase plasminogen activator (uPA), tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 expression were observed in both tumour and normal tissue samples from breast and colorectal tissue; however, expression was greater in the tumour tissue. Expression of active MMP-2 and MMP-9 and the total MMP activity were greater in tumour compared to normal samples in both tissues (P < 0.05). The expression of all proteinases and total MMP activity was greater in colorectal tissue than breast tissue samples. Breast and colorectal cancer demonstrated different proteinase profiles, however proteolysis in both tissues was greater in tumour tissue than normal tissue.

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The plasminogen-plasmin system in malignancy

Cited by 178 publications

References 221 publications

A novel function of tissue factor pathway inhibitor-2 (TFPI-2) in human glioma invasion

A novel function of tissue factor pathway inhibitor-2 (TFPI-2) in human glioma invasion

Angiostatin Generation by Cathepsin D Secreted by Human Prostate Carcinoma Cells

Proteolysis in human breast and colorectal cancer

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