The Role of Blood Platelets in Experimental Metastases

Summary Plasminogen activator (PA) is a serine protease existing in two forms known as tissue-type (t-PA) and urokinase-type (u-PA). To examine whether PA is related to the postoperative clinical course of human breast cancer, total PA activity, t-PA activity, u-PA activity, and immunoreactive t-PA were determined in tissue extracts from 144 breast cancer specimens. The patients were initially divided into four groups according to the postoperative clinical course: Group I (83 patients who are disease-free), Group II (20 patients whose first metastases were found only in bone), Group III (19 patients whose first metastases were found in both bone and lung), and Group IV (22 patients whose first metastases were found only in lung). Total PA activity was significantly lower in Groups, II, III and IV than in Group I. Both t-PA activity and t-PA antigen levels were also significantly lower in Groups II, III and IV than in Group I, while no significant difference was found in u-PA activity among these groups, indicating that low activity of total PA in Groups II, III and IV was due to a decrease in t-PA but not in u-PA. In the multivariate analyses, t-PA activity was found to be an independent prognostic factor for relapse-free survival. When four groups of patients were further analysed in terms of nodal status, both t-PA activity and antigen levels were markedly decreased in the node-negative Group II compared with the node-negative Groups III and IV or with the node-positive Groups II, III and IV. Of additional interest, u-PA activity was significantly higher in node-positive patients than in nodenegative patients with any group. The clinico-pathologic analyses of the patients in this series showed that node involvement and lymphatic invasion were more frequently positive in Groups III and IV than in Groups I and II. When 144 breast cancers were categorised in terms of combinations of oestrogen receptor (ER) and progesterone receptor (PgR) status, breast cancers which were positive for both receptors were found to contain the highest t-PA activity and antigen. This study provides provocative evidence suggesting a possible differential significance of t-PA and u-PA expression in human breast cancer.Many transformed or malignant tumour cells are known to produce plasminogen activator (PA), a serine-type protease converting plasminogen to plasmin (Unkeless et al., 1975;Howett et al., 1978;Orenstein et al., 1983). It is widely accepted that PA is intimately involved in the metastatic spread of tumour cells (Dano et al., 1985;Colombi et al., 1986;Mignatti et al., 1986;Reich et al., 1988;Ossowski et al., 1988;Markus et al., 1988;Yu et al., 1990;Testa et al., 1990;Hollas et al., 1991). There are two main forms of PA: urokinase type (u-PA) and tissue-type (t-PA). While both catalyse cleavage of the peptide bond between Arg-Val in plasminogen, thus converting the proenzyme to plasmin, they differ in many aspects such as their molecular weight, immunological reactivity and amino acid sequence (Ny et al., 1984;Riccio et al.,...

Section: Discussionmentioning

confidence: 99%

Differential biological significance of tissue-type and urokinase-type plasminogen activator in human breast cancer

Yamashita

Ogawa²,

Yamashita³

et al. 1993

“…The latter 2 types were mainly observed when tumour cells with low thromboplastic activity were injected. Hilgard (1973) considered that embolic tumour cells led to endothelial damage, inducing local thrombin formation with subsequent irreversible platelet aggregation. Platelet-aggregating activity of certain tumour cells was also recognized by some authors (Gasic et al, 1973;Tanaka et al, 1977).…”

Section: Electron-microscopic Observationsmentioning

confidence: 99%

“…The present study shows, however, no endothelial injury at the embolized sites soon after injection of tumour cells. This situation may lead to intimate participation of the tissue thromboplastin from tumour cells in aggregation of platelets and formation of fibrin, although damaged endothelial cells may participate later in adhesion and aggregation of platelets as described by Fisher et al (1967) and Hilgard (1973).…”

Section: Electron-microscopic Observationsmentioning

confidence: 99%

Lodgement and extravasation of tumour cells in blood-borne metastasis: an electron microscope study

Kinjo¹

1978

“…They do not, however, appear to have the major role in determining the fate of disseminated cells. Many factors intervene in the metastatic process, such as adhesion (Vlodavsky et al, 1982) synthesis of extracellular matrix components such as fibronectin (Neri et al, 1981), coagulation factors such as platelets (Karpatkin & Pearlstein, 1981;Hilgard, 1973), production of proteolytic enzymes (Jones & Declerck, 1980;Wang et al, 1980;Sloane et al, 1982) and other influences of the immune system. Studies in progress of the fibronectin content of these cells reveal a similar influential, but non-determinant, role in metastasis.…”

Section: Discussionmentioning

confidence: 99%

Variable susceptibility to NK activity of cloned cell lines derived from a primary rat rhabdomyosarcoma: Relationship to metastatic potential

Poupon¹,

Judde²,

Pot-Deprun³

et al. 1983

Summary In vitro cloned lines derived from a primary nickel-induced rat rhabdomyosarcoma exhibited diverse levels of susceptibility to spontaneous NK activity. The presence of NK target structures was revealed by competition assays on all cloned cell lines, and the NK susceptibility of the tumour lines varied according to their osmotic fragility. Tumour cell lines derived from metastatic lung nodules presented similar NK susceptibilities to cells originating from the primary tumour. However, cloned cell lines differed in their capacity to form lung colonies after i.v. injection, and in their potential for invading lungs after s.c. primary tumour development. No correlation was found between lung colonization potential and NK resistance. Studies of the correlation between metastatic potential and NK sensitivity revealed that (1) all the NK resistant tumour cells were highly metastatic; (2) NK susceptible tumour cells could be either highly or weakly metastatic. Therefore, highly metastatic tumour cells could be either resistant or susceptible to NK lysis. We conclude that the property of resistance to NK contributes to a high metastatic potential. However, other properties could counterbalance and finally prevail over NK susceptibility thus enabling NK susceptible cell lines to be also highly metastatic.