Kallikreins as Novel Molecular Biomarkers for Diagnosis and Prognosis of Hormone - Related Cancers

Summary: The human tissue kallikreins (KLKs, hKs) represent the largest contiguous cluster of serine protease genes in the human genome. Tissue kallikreins are encoded by 15 structurally similar, steroid hormone-regulated genes that colocalize to chromosome 19q13.4. They are widely expressed in diverse tissues and implicated in a range of normal physiologic functions from the regulation of blood pressure and electrolyte balance to tissue remodeling, prohormone processing, neural plasticity, and skin desquamation. Kallikrein function is regulated at various levels, including transcription, translation and post-translation level. It is widely known that kal-likreins are implicated in various neoplastic conditions and it has been shown that they can serve as new biomarkers for diagnosis, prognosis, and monitoring of cancer. Human Kallikrein-3 (KLK3, hK3) is the already known PSA, which has been approved as the most useful and acceptable biomarker in prostate cancer. As a consequence, many kal-likreins, in addition to hK3/PSA, have been identified as promising diagnostic and/or prognostic biomarkers for several cancer types, including ovarian, breast, and prostate. As far as prostate cancer is concerned, KLK4, KLK11, KLK14, and KLK15 genes are highly expressed. Several other kallikreins are differentially expressed at both the mRNA and protein levels in various endocrine-related malignancies, and they have prognostic value. Recent data also suggest that KLKs may be causally involved in carcinogenesis, particularly in tumor metastasis and invasion, and, thus, may represent attractive drug targets to consider for therapeutic intervention. Our data suggest that the expression analysis of the KLKs gene isoforms could also constitute novel molecular biomarkers for diagnosis, prognosis and prediction of therapy response in hormone – related cancers.

Acknowledgements: Work was supported by a Greek-Czech joint research and technology grant (EPAN.M.4.3.6.1) co-funded by the European Regional Development Fund (70%) and National Resources (30%) - Ministry of Development -General Secretariat for Research & Technology of Greece and by the Biopaths Co.