Prostate cancer (PCa) is the second most prevalent cancer among men worldwide when assessing age-standardized incidence rates. The primary method for early PCa diagnosis involves measuring the... Show moreProstate cancer (PCa) is the second most prevalent cancer among men worldwide when assessing age-standardized incidence rates. The primary method for early PCa diagnosis involves measuring the serum concentration of prostate-specific antigen (PSA), with elevated levels (> 3 ng/mL in the Netherlands) indicating the potential presence of PCa. However, the conventional PSA test exhibits a low specificity. Thus, clinical challenges persist, including the differentiation between PCa and benign prostatic hyperplasia and distinguishing indolent PCa from aggressive forms. This underscores the need for a more specific biomarker for early PCa detection and stratification. Previous studies have reported altered glycosylation features in two prostate-secreted glycoproteins, PSA and prostatic acid phosphatase (PAP) in PCa patients, e.g. variation in sialylation, fucosylation and the level of LacdiNAc . The aim of this thesis was to identify PCa biomarkers for early detection and to improve patient stratification, focusing specifically on the glycomic profiles of PSA and PAP. In addition, as PSA plays an important role with regard to fertility, its glycosylation -in relation to male infertility- was also touched upon. For this purpose, mass spectrometry (MS) based glycoproteomic methods were established to map the glycoprofiles of PSA and PAP derived from various biofluids. Show less
In this thesis, we focus on novel proteins/mechanisms that regulate integrin-adhesion mediated mechano-transduction. We characterized the role of integrin α6β4/HD and caskin2 in force generation... Show moreIn this thesis, we focus on novel proteins/mechanisms that regulate integrin-adhesion mediated mechano-transduction. We characterized the role of integrin α6β4/HD and caskin2 in force generation via FA, investigated the underlying crosstalk between adhesions and cytoskeletons. Moreover, we also explored the mechanism that drives the integrin αVβ5 clustering in FCLs, in which cell tension is also involved. Last but not the least, we investigated the role of an unexplored protein, caskin2, in the regulation of cellular mechanics. Show less
