Proteolytic Enzymes and Plasminogen Activator in Melanoma

Fräki, Jorma E.; Nieminen, S; Hopsu‐Havu, Väinö K.

doi:10.1111/j.1600-0560.1979.tb01123.x

Cited by 11 publications

(6 citation statements)

References 33 publications

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“…For various types of cancer, elevated levels of PA components have been found compared to the levels present in benign lesions or in normal tissues from corresponding histological origins 10–13. In cutaneous melanoma, PA components also seem to be involved in the malignant behaviour 14–17. Comparing melanoma lesions with common and dysplastic naevi, Delbaldo et al 15 reported an increase of mRNA levels of uPA and PAI‐1, plus the emergence of uPA‐mediated proteolysis in melanoma.…”

Section: Introductionmentioning

confidence: 99%

Spitz naevi may express components of the plasminogen activation system

Ferrier

Geloof

Straatman

et al. 2002

The Journal of Pathology

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The plasminogen activation (PA) system is involved in the process of invasion and metastasis. Its major components are urokinase (uPA) and tissue-type plasminogen activator (tPA), plasminogen activation inhibitor type 1 and 2 (PAI-1 and PAI-2) and a receptor for urokinase (uPAR). In this study, the expression of plasminogen activation components in Spitz naevi was compared with that in common and dysplastic naevi on the one hand and primary cutaneous melanomas on the other. Spitz naevi had melanocytic positivity for uPA in 0% (0/36), tPA in 30% (6/20), PAI-1 in 10% (3/35), PAI-2 in 40% (8/21) and uPAR in 60% (13/21) of cases. This far exceeded the expression found in common (n = 25) and dysplastic (n = 15) naevi, which only showed melanocytic positivity for PAI-2 (20% and 15% respectively) and in one dysplastic naevus also for uPAR. This was much (for most components significantly) less than the proportion of primary melanomas with tumour cell positivity, which was 30% (11/38) for uPA, 80% (19/24) for tPA, 75% (28/38) for PAI-1, 80% (19/24) for PAI-2 and 80% (19/24) for uPAR. The main findings of this study are that Spitz naevi, firstly, may express plasminogen activator (tPA), inhibitors and the receptor of the PA system, but in a much smaller proportion than cutaneous melanomas; and secondly, do not express urokinase, whereas some of the melanomas do. uPA positivity may therefore be suggestive of melanoma. However, overlapping staining results imply that the PA system has limited value in the differential diagnosis between Spitz naevus and primary melanoma. As serine protease components are expressed, Spitz naevi may use this proteolytic machinery to accomplish matrix degradation, although in a more restricted, possibly transient manner than melanomas.

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Section: Introductionmentioning

confidence: 99%

Spitz naevi may express components of the plasminogen activation system

Ferrier

Geloof

Straatman

et al. 2002

The Journal of Pathology

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“…The 340 subpopulations, which exhibit a higher potential for lung colonization than the 100 subpopulations, were found to have a higher CB activity, a higher CB/CPI ratio and a lower CPI activity than the 100 subpopulations [19]. Frfiki et al reported that in human melanoma tissue the BANA-hydrolysing enzyme, which corresponds to CB, has a higher activity in MM than in either PN of PM [4]. These authors therefore suggested that the increased CB activity in these subpopulations is not due to an increased synthesis but rather to a decreased regulation by endogenous CPIs [15].…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of cathepsin B-like enzyme activity and cysteine proteinase inhibitor in melanocytic tumours

et al. 1995

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We studied the relationship between cathepsin B (CB)-like enzyme activities and cysteine proteinase inhibitor (CPI) activities in lesions of human pigmented naevi (PN), primary melanomas (PM) and metastases/metastatic melanomas (MM). The CB-like enzyme activities in PM and MM were 2.5 and 6.8 times higher than in PN, respectively. The CB-like/CPI ratios in PM and MM were 1.9 and 11.6 times higher than in PN, respectively. CPI had the highest activity in PM and the lowest activity in MM. The disease-free interval of patients with a high CB-like enzyme activity (> or = 80 U/mg protein) and/or a high CB-like/CPI ratio (> or = 7) was shorter than that of patients with a low CB-like enzyme activity (< 80 U/mg protein) and/or a low CB-like/CPI ratio (< 7). Analysis of CB-like enzyme activity and/or the CB-like/CPI ratio may be useful in predicting the prognosis of human malignant melanoma.

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“…In recent years, the role of fibrinolysis in cancer growth and métastasés has attracted much attention [7,8,10]. Among the differ ent tumors, malignant melanoma received the most attention because of the observa tion that melanoma cells produce a tPA in culture.…”

Section: Discussionmentioning

confidence: 99%

“…Local fibrinoly sis, from the release of plasminogen activa tor, may result in the lysis and removal of fibrin and is believed to play a role in tumor growth and metastasis [5,6]. In recent years, a tissue plasminogen activator (tPA) has been observed in malignant melanoma tis sues [7][8][9] and in melanoma cells in culture [10][11][12] with properties similar to those of the physiological vascular tissue activator [13]. In contrast, histochemical studies of melanoma tissues by a fibrin slide method showed no gross fibrinolytic activity [14], In an attempt to resolve this apparent discrep ancy, we studied surgically obtained speci mens of melanoma tissues, several mela noma cell lines and mouse melanoma xeno grafts by the immunoperoxidase method.…”

Section: Introductionmentioning

confidence: 99%

Tissue Plasminogen Activator and Inhibitors of Fibrinolysis in Malignant Melanoma

Kwaan

Radosevich

et al. 1988

Tumor Biol

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Various human malignant tumors including malignant melanoma showed an absence of fibrinolytic activity in previous histochemical fibrin studies. In contrast, a tissue plasminogen activator has been isolated both from extracts of melanoma tissues and melanoma cell lines in culture and has been characterized to be a potent plasminogen activator. In an attempt to resolve this apparent discrepancy, we studied biopsies specimens of melanoma, several melanoma cell lines and melanoma xenografts by the immunoperoxidase method. Tissue plasminogen activator was observed in melanoma tissues, cell lines and xenografts, while various inhibitors of fibrinolysis, including α₂-antiplasmin, α₂-macroglobulin, α₁-antitrypsin and antithrombin III, were found intracellularly only in the melanoma tumor cells but not in melanoma cell lines nor in xenografts. We believe that these inhibitors are derived from the blood and are bound to the tissue plasminogen activator within the melanoma cells. Their presence in tumor cells would explain the lack of fibrinolytic activity in melanoma tissues.

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Proteolytic Enzymes and Plasminogen Activator in Melanoma

Cited by 11 publications

References 33 publications

Spitz naevi may express components of the plasminogen activation system

Spitz naevi may express components of the plasminogen activation system

Clinical relevance of cathepsin B-like enzyme activity and cysteine proteinase inhibitor in melanocytic tumours

Tissue Plasminogen Activator and Inhibitors of Fibrinolysis in Malignant Melanoma

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