Abstract
Herein, for the first time, the potential relationships between the cytoskeleton-associated proteins DAAM1 and PREP with different testicular disorders, such as classic seminoma (CS), Leydig cell tumor (LCT), and Sertoli cell-only syndrome (SOS), were evaluated. Six CS, two LCT, and two SOS tissue samples were obtained during inguinal exploration in patients with a suspect testis tumor based on clinical examination and ultrasonography. DAAM1 and PREP protein levels and immunofluorescent localization were analyzed. An increased DAAM1 protein level in CS and SOS as compared to non-pathological (NP) tissue was observed, while LCT showed no significant differences. Conversely, PREP protein level increased in LCT, while it decreased in CS and SOS compared to NP tissue. These results were strongly supported by the immunofluorescence staining, revealing an altered localization and signal intensity of DAAM1 and PREP in the analyzed samples, highlighting a perturbed cytoarchitecture. Interestingly, in LCT spermatogonia, a specific DAAM1 nuclear localization was found, probably due to an enhanced testosterone production, as confirmed by the increased protein levels of steroidogenic enzymes. Finally, although further studies are needed to verify the involvement of other formins and microtubule-associated proteins, this report raised the opportunity to indicate DAAM1 and PREP as new potential markers, supporting the cytoskeleton dynamics changes occurring during normal and/or pathological cell differentiation.
Highlights
They account for nearly 1% of all cancers in men worldwide, testicular cancers (TC) are the most common solid tumor among the 15–40 age group [34]
Our previous study using the D-Asp-treated rat model can help us to formulate this hypothesis, since we found that testicular prolyl endopeptidase (PREP) expression was enhanced, in Leydig cells (LC) and just after D-Asp treatment [30], supporting a role for PREP in the regulation of the physiological hormonal levels when they are unbalanced by the presence of Leydig cell tumor (LCT)
Analyses were performed using unpaired Students’ t-test or one-way ANOVA; Tukey’s post hoc t-test was applied when appropriate with Prism 5.0, GraphPad Software. This is the first report on the altered expression and localization of the cytoskeleton-associated proteins, Dishevelled-associated activator of morphogenesis 1 (DAAM1) and PREP, in the testicular pathologies classic seminoma (CS), LCT, and Sertoli cell-only syndrome (SOS)
Summary
The incidence rate and mortality change significantly between different countries, with the highest percentages in the most industrialized world [5]. TC frequency in the western countries has been growing, probably due to an increased exposure to environmental pollutants [6], including many endocrine-disrupting chemicals [7,8,9]. Many clinical and epidemiological data evidenced the contribution of genetic factors to their susceptibility, even though the molecular mechanism(s) underlying this association is still unclear [10,11]. It is worth remembering that among the risk factors correlated to the onset of disease, there are age, family and personal history of TC, body size, cryptorchidism, congenital abnormalities, and sub-infertility or infertility [12]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
