Description of research and teaching

Most of the research projects of the group are related to cancer biology, cell differentiation, cancer markers, and drug discovery and development. Currently, in addition to PI (Hannu Koistinen), one senior scientist (Susanna Lintula), two PhD students (Ruusu-Maaria Kovanen and Muhammad Ahmed) and one technician (Annikki Löfhjelm) are working in the group.

Prostatic proteases: Functions and targets for treatment of prostate cancer

Prostate cancer is a considerable healthcare problem that causes over 70 000 deaths annually in the EU countries alone and affects the life of 1 of every 7 man. In order to reduce the costs and side effects of treatment and to avoid unnecessary treatment, it is desirable to develop alternative non-invasive therapies and to improve the diagnostic methods.

Our main research focus is on the functions and diagnostic potential of prostatic proteases. These include known prostate cancer markers, PSA and KLK2, for which we have developed small molecule- and peptide-based stimulators and inhibitors, aiming to slow down prostate cancer growth. During recent years, we have broadened the focus to cover roles of all human proteases, i.e., degradome, and protease inhibitors in growth, invasion and metastatic spread of prostate cancer cells. This involves development of novel patient-derived cell and tissue models. The cutting-edge approach used in the project is underpinned by a wide international collaborative network. With these studies we aim to identify novel prostate cancer markers and drug target molecules. One such example is trypsin-3, which stimulates prostate cancer cell invasion and for which we have identified (with docent David Fewer) a novel potent and selective inhibitor.

The role of growth-restricting glycodelin in cancer

Glycodelin is a lipocalin family glycoprotein expressed mainly in reproductive tissues. In collaboration with William Yeung's group at University of Hong Kong we have established several reproduction related functions for glycodelin. Interestingly, these functions are regulated by glycodelin's glycosylation, i.e., different glycoforms have different activities. Based on these studies, glycodelin is considered as one of the foremost examples of how glycosylation dictates the function(s) of a glycoprotein.

More recently the group went on to show that glycodelin differentiates endometrial cancer cells towards a less aggressive phenotype, resulting in reduced tumor growth in a preclinical animal model. Interestingly, we also found that endometrial cancer glycodelin is differently glycosylated than that expressed in normal endometrium.

Techniques

Several protein chemistry, molecular biology and cell/tissue culture techniques are employed by the group. Group participates in the development of clinical assays and histochemical stainings for the studied proteins. The collaborative project in drug development offers a good perspective to drug discovery and development.

Key words: prostate cancer, cancer, castration resistant cancer, CRPC, proteases, protease inhibitors, cell invasion, metastasis, ECM, prognostic markers, cancer markers, biomarkers, cell models, tissue models, organotypic models, organoids, spheroids, translational research, histochemistry, immunoassay, assay development, RNA interference, high-throughput screening, glycosylation, glycoproteins, sperm function, fertilization, kallikreins, kallikrein-related peptidases PSA, KLK3, KLK2, trypsin, trypsin-3, mesotrypsin, PRSS3, SPINK1, hCG, glycodelin, PP14, PAEP, placental hormones.