Tumorigenesis in Mouse Skin: Inhibition by Synthetic Inhibitors of Proteases

Troll, Walter; Klassen, Arnold; Janoff, Aaron

doi:10.1126/science.169.3951.1211

Cited by 242 publications

(76 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cell division and escape from contact inhibition of growth has been demonstrated when certain proteolytic enzymes were added to confluent cultures of nonmalignant mouse fibroblasts in amounts too small to produce detachment (Burger, 1970). Conversely, inhibitors of proteolytic activity have been found to inhibit promotion by croton oil or phorbol ester of tumorigenesis in mouse skin initiated by dimethylbenzanthracene (Troll, Klassen and Janoff, 1970 (Goetz, Weinstein and Roberts, 1972).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Malignant Cell Invasion in vitro by a Proteinase Inhibitor

Latner¹,

Longstaff²,

Pradhan³

1973

Br J Cancer

View full text Add to dashboard Cite

Summary.-The inhibitory effect of the protease inhibitor aprotinin (Trasylol) on the invasion of mouse kidney explants by polyoma virus transformed BHK21 cells was investigated using a mixed cell/organ culture technique. The extent of invasion was monitored by following the changes in LDH isoenzyme pattern in the explants and by histological assessment. The kidney explants containing aprotinin were found to maintain a normal kidney LDH pattern and to suffer considerably less invasion than the explants not containing the drug. These results support the idea that proteolytic enzymes are associated with invasion and that inhibitors of protease activity could possibly be useful in the management of clinical cancer.

show abstract

Section: Methodsmentioning

confidence: 99%

Inhibition of Malignant Cell Invasion in vitro by a Proteinase Inhibitor

Latner¹,

Longstaff²,

Pradhan³

1973

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…In addition, leupeptin inhibits phytohaemagglutinin-stimulated DNA synthesis in lymphocytes (Saito et aL, 1972(Saito et aL, , 1973. This compound has also been reported to inhibit promotion by croton oil or phorbol ester of tumourigenesis in mouse skin initiated by dimethylbenzanthracene (DMBA; Troll et al, 1970;Hozumi et al, 1972). Additional protease inhibitors have also been tested for their effects on cells transformed by DMBA in vitro.…”

Section: Decreased Tumourigenic Potential Resulting From Protease Inhmentioning

confidence: 99%

Protease Inhibitors Suppress Fibrinolytic Activity of Herpesvirus-transformed Cells

Adelman¹,

Howett

Rapp

1982

Journal of General Virology

View full text Add to dashboard Cite

SUMMARYPrevious studies in this laboratory have quantified the fibrinolytic activity of herpesvirus-transformed cell lines and implicated the proteolytic capacity of cloned cell lines in the formation of primary and metastatic tumours. Because of the involvement of proteases in tumourigenesis in this system, we examined the effect of various protease inhibitors (a-1-antitrypsin, leupeptin and a-2-macroglobulin), as well as hamster serum containing acute phase proteins generated in response to physiological trauma, on the fibrinolytic capacity of a herpes simplex virus type 2-transformed hamster cell line. The effects of the various inhibitors on cell growth, fibrinolysis in vitro and tumourigenesis were examined. Leupeptin, ~-1-antitrypsin, a-2-macroglobulin and hamster serum containing acute phase proteins were capable of inhibiting fibrinolysis in vitro, were not toxic to the cells and their action was reversible, while injection of a mixture of protease inhibitor and transformed cells resulted in delayed tumour development.

show abstract

“…Consequently, it is uncertain whether antipain suppresses urethane-induced tumorigenesis by its inhibiting action on misrepair of urethaneinduced DNA damage. It may block the promotion of the preneoplastic state of cells initiated by urethane, as the protease inhibitors leupeptin and tosyl lysine chloromethyl ketone inhibit the promotion of cancer in the mouse skin after 7,12-dimethylbenz(a)anthracene (Troll et al, 1970;Hozumi et al, 1972) even though leupeptin does not seem to inhibit urethane-induced lung tumours (Matsushima et al, 1976).…”

mentioning

confidence: 99%