Tissue kallikreins: new players in normal and abnormal cell growth?

George M. Yousef; Eleftherios P. Diamandis

doi:10.1055/s-0037-1613593

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(01): 7-16
DOI: 10.1055/s-0037-1613593

Review Article

Schattauer GmbH

Tissue kallikreins: new players in normal and abnormal cell growth?

George M. Yousef

¹Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

,

Eleftherios P. Diamandis

²Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

› Author Affiliations

Abstract

Summary

Serine proteases are proteolytic enzymes with an active serine residue in their catalytic site. Kallikreins are a subgroup of the serine protease family and are known to have diverse physiological functions. The human tissue kallikrein gene family has now been fully characterized and includes 15 members, clustered in a 300 kb region on chromosome 19q13.4. In this review, we discuss the common structural features of kallik-reins at the DNA, mRNA and protein levels. Kallikreins are secreted as inactive zymogens and are activated by cleavage of an N-terminal peptide. Some kallikreins can undergo autoactivation while others may be activated by other kallikreins or other proteases. Most kallikreins are predicted to have trypsin-like enzymatic activity except for three members which may have chymotrypsin-like activity. Circumstantial evidence suggests that at least some kallikreins may be part of an enzymatic cascade pathway which is activated in aggressive forms of ovarian and probably other cancers. Accumulating evidence suggests potential diagnostic and/or prognostic roles of kallikreins in diverse malignancies. In addition to PSA, many other kallik-reins show differential expression in malignancy. For example, hK6, 10 and 11 are promising serological markers for ovarian cancer diagnosis. KLK10 may act as a tumor suppressor. In addition to their diagnostic and prognostic values, kallikreins may also be good therapeutic targets.

Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

Keywords

Kallikreins - tumor markers - prostate cancer - breast cancer - ovarian cancer - serine proteases - prognostic and predictive markers

Full Text

References

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