Table 1.

Overview of antitumorigenic proteins with tPA-stimulating activity


Protein

Effect on angiogenesis or tumor growth

Stimulation of tPA-mediated plasminogen activation
Endostatin   O'Reilly et al, 1997  Reijerkerk et al, 200317  
Thrombospondin*  Volpert et al, 199862   Silverstein et al, 1984, 1985, 198663-65  
Angiostatin  O'Reilly et al, 1994  Unknown  
Denatured antithrombin III   O'Reilly et al, 1999  Machovich and Owen, 199739  
Prothrombin fragments   Rhim et al, 1998  Machovic et al, 199966  
βpep25 (Anginex)   Griffioen et al, 200167   A.R., unpublished  
Maspin   Zou et al, 199468   Sheng et al, 199869  
Histidine-proline-rich glycoprotein   Juarez et al, 200270   Silverstein et al, 198563 ; Borza and Morgan, 199771  
Fibrin(ogen) degradation products   AR unpublished and Brown et al, 2002  Stewart et al, 199872  
Calreticulin (fragments), vasostatin   Pike et al, 199973   Binds tPA. Allen and Bulleid, 199774  
Amphoterin
 
Huttunen et al, 200255 
 
Parkinen and Rauvala, 199175 
 

Protein

Effect on angiogenesis or tumor growth

Stimulation of tPA-mediated plasminogen activation
Endostatin   O'Reilly et al, 1997  Reijerkerk et al, 200317  
Thrombospondin*  Volpert et al, 199862   Silverstein et al, 1984, 1985, 198663-65  
Angiostatin  O'Reilly et al, 1994  Unknown  
Denatured antithrombin III   O'Reilly et al, 1999  Machovich and Owen, 199739  
Prothrombin fragments   Rhim et al, 1998  Machovic et al, 199966  
βpep25 (Anginex)   Griffioen et al, 200167   A.R., unpublished  
Maspin   Zou et al, 199468   Sheng et al, 199869  
Histidine-proline-rich glycoprotein   Juarez et al, 200270   Silverstein et al, 198563 ; Borza and Morgan, 199771  
Fibrin(ogen) degradation products   AR unpublished and Brown et al, 2002  Stewart et al, 199872  
Calreticulin (fragments), vasostatin   Pike et al, 199973   Binds tPA. Allen and Bulleid, 199774  
Amphoterin
 
Huttunen et al, 200255 
 
Parkinen and Rauvala, 199175 
 
*

Thrombospondin also binds the multiligand receptor CD36.56,76 

Angiostatin that is tested in clinical trials is made in P pastoris. The original experiments, however, were performed with angiostatin prepared by proteolytic cleavage with elastase, followed by purification on a lysine-Sepharose column and subsequent dialysis against H2O. The latter method of purification leaves the possibility that fragments are present with amyloid properties. We, therefore, suggest that different forms of angiostatin may also yield differences in bioactivity.

Amphoterin also binds the multiligand receptor RAGE.55 

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