Background/Aim: Vimentin3 (Vim3) was recently described as a tumour marker for the direct discrimination between benign and malignant kidney tumours. Here, we examined its expression in prostate cancer (PCa) cell lines and the regulation of its expression by endothelin receptors. Materials and Methods: Prostate cancer cell lines (PC3, DU145, LNCap) were incubated with endothelin 1 (ET-1), BQ123 [endothelin A receptor (ETAR) antagonist], BQ788 [endothelin B receptor (ETBR) antagonist], BQ123+ET-1, BQ788+ET-1 for 24 h and a scratch assay was performed.Cell extracts were analysed by western blotting and qRT-PCR. Results: ET-1 induced Vim3 overexpression. Blocking the ETBR in the different prostate cancer cell lines yielded a higher migration rate, whereby Vim3 expression was significantly increased. Conclusion: Vim3 concentration increases in cell lines without a functional ETBR and may be used as a marker for PCas where ETBR is frequently methylated.
349 Background: An upregulation of vimentin 3, a truncated version of the full length vimentin, with an unknown function, was previously described by our group, in a direct dependency of increased ET-1 levels. We analyzed now vimentin 3 in further genitourinary cancers. Here, we describe our findings how vimentin 3 is part of the signaling pathways from Endothelin-1 (ET-1) and the Endothelin-A-Receptor (ETAR) and how it correlates with aggressive tumor behavior in a PCa cell culture and in human tissue and serum samples from PCa patients. Methods: DU145 cells were cultured. We stimulated with ET-1 with and without artificial downregulation of the ETAR, the ETBR or both receptors. A scratch assay was performed to demonstrate the influence of ET-1. Proteins were then extracted and WB for vimentin full length and vimentin 3 was performed. Additionally we analyzed ET-1 and vimentin 3 in serum from prostate cancer patients using ELISA and we did IF and IHC staining for vimentin 3 in human prostate cancer tissue. Results: Treatment with ET-1 and downregulation of the ETBR lead to a significant increased migration of DU145 cells after 3 and 6 h. The corresponding WB showed increased vimentin 3. ELISA showed increased levels of ET-1 in samples of prostate cancer patients compared to patients with no cancer history. ELISA could also demonstrate elevated levels of vimentin 3 in serum of patients with local disease and significantly elevated values in metastatic prostate cancer patients compared to patients with no cancer history. Conclusions: The data presented shows that ET-1 stimulation leads to overexpression of vimentin 3 in prostate cancer cell cultures and a concomitant aggressive biological behavior. Here we previously described the direct interaction of Vimentin 3 in prostate cancer and the activation mechanism via ET-1 and the ETAR. IHC, IF show an upregulation of the truncated variant Vimentin3 in tissue samples. In an Vimentin 3 ELISA we could show that this truncated variant is increased and therefore represents a potential biomarker. Highest values of vimentin 3 were measured using ELISA in serum of patients with recurrent and metastatic disease also suggesting that vimentin 3 correlates with aggressive tumor behavior.
Background: Vimentin3 (Vim3) was recently described as a tumor marker for the direct differentiation between benign and malignant kidney tumors. Our group recently reported correlation between Vim3 overexpression and increasing migration of PCa cell lines.Objectives: Comparing Vim3 serum levels among different PCa grades.Design Setting and Participants: serum samples obtained. from PCa patients (n=314) between 2017 and 2020 were classified according to the grade group system and analysed by ELISA, and Western Blot to measure Vim3 levels. Additionally, Paraffin embedded human PCa samples from radical prostatectomy specimens were stained immunohistochemically for Vim3 (n=10).Outcome Measurements and Statistical Analysis: Vim3 levels in serum samples show a correlation with increasing aggressiveness of PCas. ANOVA analysis was used.Results and limitations: the Vim3 protein level increased significantly (p<0.001) with increasing biological aggressiveness of human PCa specimens from prostate biopsies and/or radical prostatectomy specimens (Gleason ≥8). A "grey-zone" value for Vim3 was determined (300-350 ng/ml). Furthermore, Vim3 levels in the Gleason >7 group (3+4) (4+3), metastasis, castration resistant and castration responder was analysed. Vim3 levels significantly decrease in the group of ADT responders. Limitations include the retrospective and single centre design. Conclusion:Vim3 could be a new surrogate biomarker for the classification and graduation of PCa, especially for PCa with increasing metastatic potential. Additionally, we hypothesised that Vim3 determination can be usable for ADT respond control.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.