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

Kinjo, Mitsuru

doi:10.1038/bjc.1978.201

Cited by 61 publications

(29 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, it has been stressed that the most important factors influencing the ability to form fibrin with clumping of tumour cells would be fibrinolytic activity of tumour cells themselves rather than that of blood itself (Warren, 1973;Kinjo, 1978). While both t-PA and u-PA cleave the same single peptide bond in plasminogen to convert it into plasmin, t-PA is distinguished by its high affinity for fibrin.…”

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

Br J Cancer

View full text Add to dashboard Cite

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.,...

show abstract

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

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…The non-receptor tyrosine kinase Src, the first identified oncogene (see Guarino, 2010;Irby and Yeatman, 2000 for review), induces the formation of invadopodia (see Murphy and Courtneidge, 2011 for review), which are dynamic and actin-rich protrusions detected in many highly invasive cancer cell lines derived from solid tumors such as breast, melanoma and fibrosarcoma (Linder et al, 2011;Murphy and Courtneidge, 2011). Invadopodia are enriched in matrix-metalloproteases (MMPs) and are necessary at many stages of the metastatic process such as breaking through the basement membrane (Kinjo, 1978) and extravasating through blood vessels (Leong et al, 2014;see Lohmer et al, 2014;Paz et al, 2014 for review). Invadopodia are regulated downstream of many RhoGTPases for review), formed downstream of Src activation (Chen et al, 1985) and induced in response to a variety of external stimuli (see Linder et al, 2011;Murphy and Courtneidge, 2011 for review).…”

Section: Introductionmentioning

confidence: 99%

Sorting nexin 9 negatively regulates invadopodia formation and function in cancer cells

Bendris

Stearns

Reis

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

The ability of cancer cells to degrade the extracellular matrix and invade interstitial tissues contributes to their metastatic potential. We recently showed that overexpression of sorting nexin 9 (SNX9) leads to increased cell invasion and metastasis in animal models, which correlates with increased SNX9 protein expression in metastases from human mammary cancers. Here, we report that SNX9 expression is reduced relative to neighboring normal tissues in primary breast tumors, and progressively reduced in more aggressive stages of non-small-cell lung cancers. We show that SNX9 is localized at invadopodia where it directly binds the invadopodia marker TKS5 and negatively regulates invadopodia formation and function. SNX9 depletion increases invadopodia number and the local recruitment of MT1-MMP by decreasing its internalization. Together, these effects result in increased localized matrix degradation. We further identify SNX9 as a Src kinase substrate and show that this phosphorylation is important for SNX9 activity in regulating cell invasion, but is dispensable for its function in regulating invadopodia. The diversified changes associated with SNX9 expression in cancer highlight its importance as a central regulator of cancer cell behavior.

show abstract

“…Several reports (Peterson, 1968;Tanaka et al, 1977;Clark, 1979;Donati et al, 1978) have suggested that the coagulation-fibrinolysis system plays different roles in the various stages of metastasis. Some workers (Jones et al, 1971;Warren & Vales, 1972;Chew & Wallace, 1976;Kinjo, 1978) have demonstrated the association of fibrin with tumour-cell emboli in distant organs. Fibrin formation may aid in tumour arrest and adherence to blood vessel endothelium.…”

mentioning

confidence: 99%

Ultrastructural study of the effects of tranexamic acid and urokinase on metastasis of Lewis lung carcinoma

Tanaka¹,

Ogawa²,

Kinjo³

et al. 1982

Br J Cancer

Self Cite

View full text Add to dashboard Cite

Summary.-Lewis lung carcinoma cells were implanted in the foot-pads of mice and the effects of the plasminogen-plasmin inhibitor tranexamic acid (t-AMCHA) and of the plasminogen activator urokinase on metastasis were examined by electron microscopy. The intravascular tumour cells were not associated with thrombus formation in either control or urokinase -treated mice. Polymerized fibrin deposition around tumour cells and thrombi composed of fibrin and platelets was observed only in the mice given t-AMCHA. This suggests that the inhibition of fibrinolysis by tACC caused fibrin deposition and thrombus formation around intravascular tumour cells, which prevented release of the cells from primary foci to form secondary tumours. On the other hand, fibrinolysis induced by urokinase prevented thrombus formation, and accelerated cell release from primary foci.

show abstract

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

Abstract: These results indicate that thromboplastic activity of tumour cells might be important in forming microthrombi in the lodgement phase and might be one of the factors facilitating blood-borne metastasis.

Cited by 61 publications

References 7 publications

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

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

Sorting nexin 9 negatively regulates invadopodia formation and function in cancer cells

Ultrastructural study of the effects of tranexamic acid and urokinase on metastasis of Lewis lung carcinoma

Contact Info

Product

Resources

About