The Plasminogen Activation System in Tumour Invasion and Metastasis

Vries, T.J. de; Muijen, G.N.P. van; Ruiter, Dirk J.

doi:10.1016/s0344-0338(96)80094-x

Cited by 39 publications

(27 citation statements)

References 156 publications

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“…TF, which we showed to be overexpressed by malignant cell prostasomes, is known of playing additional biological roles, including the promotion of tumor angiogenesis [111,152], cell adhesion [153], cell migration [154] and tumor cell invasion [155]. Furthermore, it binds to plasminogen with high affinity [156] an effector which may play a role in the enhancement of tumor growth and metastasis [157,158]. Suppression of fibrinolysis is important for metastatic prostate cancer cells.…”

Section: H Procoagulant Effect Of Prostasomes and Overexpression Of mentioning

confidence: 91%

Prostasome Involvement in the Development and Growth of Prostate Cancer~!2009-07-10~!2009-12-09~!2010-02-11~!

Babiker¹,

Ronquist²,

Nilsson³

et al. 2010

TOPCANJ

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Prostasomes are extracellularly occurring submicron, membrane-surrounded organelles produced by the epithelial cells of the prostate and present in semen after secretion. Even dedifferentiated prostate cancer cells have preserved their ability to produce and export prostasomes to the extracellular space. The precise physiological role of prostasomes is not known, although some of their properties assign them to important physiological and patho-physiological functions that could be exploited in prostate cancer growth and development. In this review, some new properties of seminal and malignant cell line (DU145, PC-3 and LNCaP) prostasomes will be discussed.There are typical differences in the expressions and activities of prostasomal CD59, ATPase, protein kinases and tissue factor (TF) as well as in the transfer of prostasomal CD59 to CD59-deficient erythrocytes (rabbit and human PNH erythrocytes). CD59, protein kinases and TF exhibit characteristic patterns of overexpression by malignant cell prostasomes. A high ATPase activity is recognized on seminal prostasomes with minimal activity on malignant cell prostasomes resulting in more residual ATP available for phosphorylation reactions. Several proteins are phosphorylated by prostasomal protein kinases, namely, complement component C3, fibrinogen, vitronectin and E-cadherin. Furthermore, TF is identified as the main endogenous phosphorylation substrate on prostasomes. In addition, prothrombotic effects of prostasomes are demonstrated. DU145 and PC-3 cell-derived prostasomes exert a higher clotting effect on whole blood and plasma compared to LNCaP cell-derived and seminal prostasomes.In conclusion, malignant cell prostasomes show an increased ability to interact with the biological system in favor of prostate cancer cell promotion and survival. The roles played by prostasomes in this context may improve the understanding of the mechanisms that help the prostate cancer cells to avoid the complement attack (CD59 transfer and phosphorylation and inactivation of C3), to promote angiogenesis (TF) and to metastasize. It may also provide a better understanding of some of the complications usually seen in some terminal prostate cancer patients like thrombotic events and tendency to develop disseminated intravascular coagulation.Keywords: ATPase, CD59, CK, complement, DU145, Extracellular phosphorylation, LNCaP, PC-3, PKA, PKC, prostasomes, prostate cancer, protein kinases, tissue factor. I. GENERAL BACKGROUND A. Prostate CancerProstate cancer is the most prevalent noncutaneous cancer in many of the Western countries and is the second leading cause of cancer death in men in USA [1]. The introduction of prostate specific antigen (PSA) in the latter half of 1980s as a biochemical marker of prostate cancer in serum signified a radical change of the pattern of prostate cancer diagnosis. It meant that more cases were detected at an early stage and substantially fewer at advanced stages [2] [3]. There are also studies showing that increasing incidence of prostate can...

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Section: H Procoagulant Effect Of Prostasomes and Overexpression Of mentioning

confidence: 91%

Prostasome Involvement in the Development and Growth of Prostate Cancer~!2009-07-10~!2009-12-09~!2010-02-11~!

Babiker¹,

Ronquist²,

Nilsson³

et al. 2010

TOPCANJ

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“…84,85 Results obtained on the highly invasive 1-LN human prostate tumour cell line provided new evidence connecting DPP IV with the activation of plasminogen and the expression of matrix metalloproteinase-9 86 thus bringing about a degradation of extracellular matrix components and facilitating cancer invasion.…”

Section: Invasive Supportmentioning

confidence: 99%

“…105 These actions may contribute to the roles that tissue factor and plasminogen play in the enhancement of tumour growth and metastasis. 85,106 Angiogenetic capacity Tissue factor promotes angiogenesis through a mechanism involving the formation of a complex with activated factor VII (factor VIIa), which generates activated factor X (factor Xa), leading to the activation of thrombin that then stimulates the production of vascular endothelial growth factor. 107 As a matter of fact, immunohistochemical analysis of prostate cancer specimens localized tissue factor expression to the epithelial cells 108 that also express prostasomes.…”

Section: Invasive Supportmentioning

confidence: 99%

The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and malignant prostate growth

Ronquist

Nilsson

2004

Prostate Cancer Prostatic Dis

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Prostasomes are submicron secretory granules synthesized, stored and secreted by the epithelial cells of the human prostate gland. They are membrane-surrounded also in their extracellular appearance and the membrane architecture is composite. They are believed to be life-giving and act as protectors of the spermatozoa in the lower and upper female genital tract on their way to the ovum. Hence, the prostasomes are immunosuppressive and inhibitory of complement activation. Further, they promote sperm's forward motility and have antioxidant and antibacterial capacities. The prostasomes with their many composite abilities seem to turn against the host cell after the age of 50 y being conducive to the transition of the normal prostate epithelial cell into a neoplastic cell and therewith lay the foundations of the very high prevalence of prostate cancer of men of more than 50 y of age. Prostate Cancer and Prostatic Diseases (2004) 7, 21-31. doi:10.1038/sj.pcan.4500684 Keywords: prostasomes Prostate cancerProstate cancer is the most common cancer in men in Europe, North America, and some parts of Africa. Incidence of prostate cancer is increasing steadily in most countries. Incidence and death rates differ according to race and geographical location. 1 Different autopsy studies performed in Western and Oriental populations have shown that the prevalence of prostate cancer is significantly higher than its incidence. Comparative assessments of these studies have provided similar prevalence rates in different races and geographical areas. 2 The differences in the incidence of prostate cancer in different races and geographical areas and the different progression of this incidence in populations of a race living in a foreign geographical area, strengthen the hypothesis that genetic and lifestyle factors are responsible for the difference in post-induction progression of prostate cancer. 3,4 The incidence rate of clinically apparent prostate cancer is eight-fold higher in the United States than in Japan, while the prevalence of latent prostate cancer, a presumed precursor of clinical prostate cancer, is similar in the two countries. 5 However, the initiating and promoting factors that determine the variability in the natural history of prostate cancer remain unknown. 6 There is a substantial discrepancy between the high incidence of prostate cancer and the extremely low incidence of primary cancer in the seminal vesicles, 7 although the two glands represent neighbouring anatomical locations, both of them being exocrine accessory genital glands and both being under similar hormonal control. Hence, there may be endogenous as well as exogenous factors promotive of prostate cancer development. We hypothesize that prostasomes with their exclusive origin in the prostate gland and with their Received

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“…uPA and PAI-1 have been involved in intracellular signaling through uPAR (Konakova et al 1998). Besides its role in normal physiological processes, such as tissue remodeling, cell migration, and wound healing, the plasminogen activation system is associated with tumor invasiveness and metastasis and both, uPA and PAI, can be overexpressed in tumor cells or neighboring tissue (de Vries et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Modulation of urokinase plasminogen activator system by poly(ADP-ribose)polymerase-1 inhibition

et al. 2014

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The urokinase plasminogen activator (uPA) system is a complex regulator of extracellular proteolysis which is involved in various physiological and pathological processes. The major components of this system are the serine protease uPA, two inhibitors PAI-1 and PAI-2, and the receptor uPAR. It has been previously shown by several groups that the uPA system has an important role in cancer progression and therefore its possible prognostic and therapeutic value has been evaluated. The aim of this study is to tackle the role of poly(ADP-ribosyl)ation in the induction of uPA activity in a glioblastoma cell line, A1235. This cell line is sensitive to alkylation damage and is a model for drug treatment. The components of the uPA system and the level of DNA damage were analyzed after alkylation agent treatment in combination with poly(ADP-ribose)polymerase-1 (PARP-1) inhibition. Here we show that the increase in uPA activity results from the net balance change between uPA and its inhibitor at mRNA level. Further, PARP-1 inhibition exerts its influence on uPA activity through DNA damage increase. Involvement of several signaling pathways, as well as cell specific regulation influencing the uPA system are discussed.

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The Plasminogen Activation System in Tumour Invasion and Metastasis

Abstract: SUMMARY The involvement o f proteases in the metastatic spread o f tumour cells and in tumour

Cited by 39 publications

References 156 publications

Prostasome Involvement in the Development and Growth of Prostate Cancer~!2009-07-10~!2009-12-09~!2010-02-11~!

Prostasome Involvement in the Development and Growth of Prostate Cancer~!2009-07-10~!2009-12-09~!2010-02-11~!

The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and malignant prostate growth

Modulation of urokinase plasminogen activator system by poly(ADP-ribose)polymerase-1 inhibition

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