Blood-based detection of MMP11 - as a marker of prostate cancer progression regulated by the ALDH1A1-TGF-β1 signaling mechanism

Sep 23, 2026

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Prostate cancer remains difficult to treat once metastatic disease progresses, with no curative options and limited clinical tests to predict dissemination and therapeutic response. This study investigates how ALDH1A1 and ALDH1A3 regulate metastatic mechanisms, focusing on whether plasma biomarkers can reflect these pathways. The research tests RAR/AR-driven control of TGFβ1 and links expression and plasma protein levels of MMP11 to pathological parameters and clinical outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages25

Reading Time1 h 3 min

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Abstract

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Gorodetska et al. J Exp Clin Cancer Res (2025) 44:105 [https://doi.org/10.1186/s13046-025-03299-6](https://doi.org/10.1186/s13046-025-03299-6) Journal of Experimental & Clinical Cancer Research RESEARCH Open Access Blood-based detection of MMP11 as a marker of prostate cancer progression regulated by the ALDH1A1-TGF-β1 signaling mechanism Ielizaveta Gorodetska1,2, Vasyl Lukiyanchuk 1,2, Marta Gawin3, Myroslava Sliusar1,2, Annett Linge1,4,5,6,7, Fabian Lohaus 1,4,5,6, Tobias Hölscher 1,6,7, Kati Erdmann4,8, Susanne Fuessel4,8, Angelika Borkowetz4,8, Anna Wojakowska9, Daniel Fochtman9, Mark Reardon10, Ananya Choudhury10, Yasmin Antonelli11, Aldo Leal‑Egaña 11, Ayse Sedef Köseer1,2,7, Uğur Kahya1,2, Jakob Püschel 1, Andrea Petzold 1, Daria Klusa 1,7, Claudia Peitzsch1,4,7,12, Romy Kronstein‑Wiedemann13,14, Torsten Tonn4,13,14, Lukasz Marczak9, Christian Thomas4,7,8, Piotr Widłak15, Monika Pietrowska3, Mechthild Krause 1,2,4,5,6,7 and Anna Dubrovska 1,2,4,5,7* Abstract Background Prostate cancer (PCa) is the second most common type of tumor diagnosed in men and the fifth leading cause of cancer‑related death in male patients. The response of metastatic disease to standard treatment is heterogeneous. As for now, there is no curative treatment option available for metastatic PCa, and the clinical tests capable of predicting metastatic dissemination and metastatic response to the therapies are lacking. Our recent study identified aldehyde dehydrogenases ALDH1A1 and ALDH1A3 as critical regulators of PCa metastases. Still, the exact mechanisms mediating the role of these proteins in PCa metastatic dissemination remain not fully understood, and plasma‑based biomarkers of these metastatic mechanisms are not available. Methods Genetic silencing, gene overexpression, or treatment with different concentrations ofthe retinoic acid (RA) isomers, which are the products of ALDH catalytic activity, were used to modulate the interplay between retinoic acid receptors (RARs) and androgen receptor (AR) . RNA sequencing (RNAseq), reporter gene assays, and chromatin immu‑ noprecipitation (ChIP) analysis were employed to validate the role of RARs and AR in the regulation of the transform‑ ing growth factor‑beta 1 (TGFB1) expression. Gene expression levels of ALDH1A1, ALDH1A3, and the matrix metal‑ loproteinase 11 (MMP11) and their correlation with pathological parameters and clinical outcomes were analysed by mining several publicly available patient datasets as well as our multi‑center transcriptomic dataset from patients with high‑risk and locally advanced PCa. The level of MMP11 protein was analysed by enzyme‑linked immunosorbent assay (ELISA) in independent cohorts of plasma samples from patients with primary or metastatic PCa and healthy donors, while plasma proteome profiles were obtained for selected subsets of PCa patients. *Correspondence: Anna Dubrovska[a.dubrovska@hzdr.de](a.dubrovska@hzdr.de) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication wai

FAQs

What clinical problem does the study address in metastatic prostate cancer?

Metastatic prostate cancer lacks curative treatment options and reliable clinical tests to predict dissemination and response to therapy.

How is MMP11 evaluated in relation to prostate cancer progression?

MMP11 expression is assessed by mining patient datasets and transcriptomic data, while MMP11 protein levels in plasma are measured using ELISA and related to clinical outcomes.

What signaling mechanism is proposed to regulate MMP11 and progression?

The study supports a pathway where TGF-β1 signaling contributes to regulation of MMPs, including MMP11, in an ALDH1A1-driven metastatic context.

Sep 23, 2026

Uploaded by Levi