scholarly journals The Multifaceted Role of Plasminogen in Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2304
Author(s):  
Beate Heissig ◽  
Yousef Salama ◽  
Taro Osada ◽  
Ko Okumura ◽  
Koichi Hattori

Fibrinolytic factors like plasminogen, tissue-type plasminogen activator (tPA), and urokinase plasminogen activator (uPA) dissolve clots. Though mere extracellular-matrix-degrading enzymes, fibrinolytic factors interfere with many processes during primary cancer growth and metastasis. Their many receptors give them access to cellular functions that tumor cells have widely exploited to promote tumor cell survival, growth, and metastatic abilities. They give cancer cells tools to ensure their own survival by interfering with the signaling pathways involved in senescence, anoikis, and autophagy. They can also directly promote primary tumor growth and metastasis, and endow tumor cells with mechanisms to evade myelosuppression, thus acquiring drug resistance. In this review, recent studies on the role fibrinolytic factors play in metastasis and controlling cell-death-associated processes are presented, along with studies that describe how cancer cells have exploited plasminogen receptors to escape myelosuppression.

1999 ◽  
Vol 81 (04) ◽  
pp. 601-604 ◽  
Author(s):  
Hiroyuki Matsuno ◽  
Osamu Kozawa ◽  
Masayuki Niwa ◽  
Shigeru Ueshima ◽  
Osamu Matsuo ◽  
...  

SummaryThe role of fibrinolytic system components in thrombus formation and removal in vivo was investigated in groups of six mice deficient in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), or plasminogen activator inhibitor-1 (PAI-1) (u-PA-/-, t-PA-/- or PAI-1-/-, respectively) or of their wild type controls (u-PA+/+, t-PA+/+ or PAI-1+/+). Thrombus was induced in the murine carotid artery by endothelial injury using the photochemical reaction between rose bengal and green light (540 nm). Blood flow was continuously monitored for 90 min on day 0 and for 20 min on days 1, 2 and 3. The times to occlusion after the initiation of endothelial injury in u-PA+/+, t-PA+/+ or PAI-1+/+ mice were 9.4 ± 1.3, 9.8 ± 1.1 or 9.7 ± 1.6 min, respectively. u-PA-/- and t-PA-/- mice were indistinguishable from controls, whereas that of PAI-1-/- mice were significantly prolonged (18.4 ± 3.7 min). Occlusion persisted for the initial 90 min observation period in 10 of 18 wild type mice and was followed by cyclic reflow and reocclusion in the remaining 8 mice. At day 1, persistent occlusion was observed in 1 wild type mouse, 8 mice had cyclic reflow and reocclusion and 9 mice had persistent reflow. At day 2, all injured arteries had persistent reflow. Persistent occlusion for 90 min on day 0 was observed in 3 u-PA-/-, in all t-PA-/- mice at day 1 and in 2 of the t-PA-/-mice at day 2 (p <0.01 versus wild type mice). Persistent patency was observed in all PAI-1-/- mice at day 1 and in 5 of the 6 u-PA-/- mice at day 2 (both p <0.05 versus wild type mice). In conclusion, t-PA increases the rate of clot lysis after endothelial injury, PAI-1 reduces the time to occlusion and delays clot lysis, whereas u-PA has little effect on thrombus formation and spontaneous lysis.


Hepatology ◽  
1992 ◽  
Vol 16 (2) ◽  
pp. 404-408 ◽  
Author(s):  
C. Minke Bakker ◽  
Herold J. Metselaar ◽  
Theo N. Groenland ◽  
Maria J. Gomes ◽  
Eduard A. R. Knot ◽  
...  

1989 ◽  
Vol 3 (4) ◽  
pp. 207-214 ◽  
Author(s):  
M.J. Browne ◽  
C.G. Chapman ◽  
I. Dodd ◽  
B. Reavy ◽  
A.F. Esmail ◽  
...  

2013 ◽  
Vol 25 (1) ◽  
pp. 247
Author(s):  
M. J. Izquierdo-Rico ◽  
M. Moreno-Manrique ◽  
F. A. García-Vázquez ◽  
M. J. Sánchez-Calabuig ◽  
P. Coy

Tissue-type plasminogen activator (tPA) is one of the components of the plasminogen-plasmin (PLG-PLA) system, better known as fibrinolytic system for its role in the blood clot lysis. It has been demonstrated recently that the activation of plasminogen into the protease plasmin during the sperm-oocyte interaction in the pig and cow decreases the percentages of penetration and increases monospermy (Mondéjar et al. 2012). However, in the mouse species, it was showed that PLG-PLA system enhances fertilization (Huarte et al. 1993). Expression of tPA has been described in rat oocytes (Bicsak et al. 1989) and cumulus cells (Ny et al. 1987; O’Connell et al. 1987), but no clear evidence about its expression in mouse, pig, and cow oocytes or cumulus cells is available. We hypothesised that differences in the effect of PLG-PLA system on fertilization results between the species mentioned above could be related to differences in tPA expression. The aim of this study was the detection of mRNA encoding tPA in oocytes and cumulus cells in mouse, pig, and cow by molecular analysis. Total RNA was obtained from oocytes and cumulus cells and cDNA was synthesised with an oligo-dT as primer. These cDNAs were used as template in RT-PCR amplifications using specific primers designed based on the GenBank sequence for Mus musculus, Sus scrofa, and Bos taurus tPA (NM_ 008872, NM_214054, NM_174146, respectively). The results of this study showed a different expression in the 3 studied species. In mouse, amplicon encoding tPA was detected in oocytes and cumulus cells. In cow and pig, tPA transcripts were obtained only in cumulus cells. The relation between the differences in the tPA expression pattern and the role of PLG-PLA system on fertilization remains to be investigated. This study was supported by MICINN (AGL2009-12512-C02-01-02).


2002 ◽  
Vol 87 (02) ◽  
pp. 306-310 ◽  
Author(s):  
P.E. Morange ◽  
D. Bastelica ◽  
M.F. Bonzi ◽  
B. Van Hoef ◽  
D. Collen ◽  
...  

SummaryTo investigate the potential role of tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA) in development of adipose tissue, we have used a nutritionally induced obesity model in t-PA (t-PA−/−) and u-PA (u-PA−/−) deficient mice. Five week old male wild-type (WT), t-PA−/− or u-PA−/− mice (n = 9 to 16) were fed a high fat diet (HFD, 42% fat). After 16 weeks of HFD, the body weight of t-PA−/− mice was significantly higher than that of WT mice (48 ± 1.1 g vs. 39 ± 2.2 g, p = 0.004). The total weight of the isolated subcutaneous (sc) fat deposit was higher in t-PA−/− than in WT mice (2.4 ± 0.22 g vs. 1.2 ± 0.29 g, p = 0.002), accompanied with higher adipocyte diameters (80 ± 1.7 µm vs. 61 ± 4.7 µm, p < 0.01). These differences were not observed in the intra-abdominal fat deposit. The number of stroma cells in both adipose tissue territories was increased in t-PA−/− as compared to WT mice (2.0 ± 0.13 vs. 1.5 ± 0.10 p = 0.02 and 3.0 ± 0.17 vs 1.6 ± 0.17, p = 0.0001, stroma cells/ adipocytes in sc and intra-abdominal tissue, respectively), partly as a result of an increased number of endothelial cells (192 ± 9 vs. 154 ± 18 p = 0.06 and 108 ± 13 vs. 69 ± 8 p = 0.04 CD31 stained/adipocyte area). In contrast the weight gain and adipose tissue development in u-PA−/− mice was not different from that in WT mice. These data suggest that t-PA but not u-PA plays a role in adipose tissue development.


1994 ◽  
Vol 9 (4) ◽  
pp. 251-253 ◽  
Author(s):  
A. Ruibal ◽  
A. Alvarez ◽  
B. Fernández Llana ◽  
Ma Fernández Fernández ◽  
Ma C. Roiz ◽  
...  

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