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@ARTICLE{Gorodetska:300112,
author = {I. Gorodetska and V. Lukiyanchuk and M. Gawin and M.
Sliusar and A. Linge$^*$ and F. Lohaus$^*$ and T. Hölscher
and K. Erdmann$^*$ and S. Fuessel$^*$ and A. Borkowetz$^*$
and A. Wojakowska and D. Fochtman and M. Reardon and A.
Choudhury and Y. Antonelli and A. Leal-Egaña and A. S.
Köseer and U. Kahya and J. Püschel and A. Petzold and D.
Klusa and C. Peitzsch$^*$ and R. Kronstein-Wiedemann and T.
Tonn$^*$ and L. Marczak and C. Thomas$^*$ and P. Widłak and
M. Pietrowska and M. Krause$^*$ and A. Dubrovska$^*$},
title = {{B}lood-based detection of {MMP}11 as a marker of prostate
cancer progression regulated by the {ALDH}1{A}1-{TGF}-β1
signaling mechanism.},
journal = {Journal of experimental $\&$ clinical cancer research},
volume = {44},
number = {1},
issn = {0392-9078},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2025-00610},
pages = {105},
year = {2025},
abstract = {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.Genetic silencing, gene overexpression, or
treatment with different concentrations of the 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
immunoprecipitation (ChIP) analysis were employed to
validate the role of RARs and AR in the regulation of the
transforming growth factor-beta 1 (TGFB1) expression. Gene
expression levels of ALDH1A1, ALDH1A3, and the matrix
metalloproteinase 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.We could show that ALDH1A1 and
ALDH1A3 genes differently regulate TGFB1 expression in a
RAR- and AR-dependent manner. We further observed that the
TGF-β1 pathway contributes to the regulation of the MMPs,
including MMP11. We have confirmed the relevance of MMP11 as
a promising clinical marker for PCa using several
independent gene expression datasets. Further, we have
validated plasma MMP11 level as a prognostic biomarker in
patients with metastatic PCa. Finally, we proposed a
hypothetical ALDH1A1/MMP11-related plasma proteome-based
prognostic signature.TGFB1/MMP11 signaling contributes to
the ALDH1A1-driven PCa metastases. MMP11 is a promising
blood-based biomarker of PCa progression.},
keywords = {Humans / Male / Prostatic Neoplasms: pathology / Prostatic
Neoplasms: genetics / Prostatic Neoplasms: metabolism /
Aldehyde Dehydrogenase 1 Family: metabolism / Aldehyde
Dehydrogenase 1 Family: genetics / Retinal Dehydrogenase:
metabolism / Retinal Dehydrogenase: genetics / Biomarkers,
Tumor: metabolism / Biomarkers, Tumor: genetics / Signal
Transduction / Transforming Growth Factor beta1: metabolism
/ Transforming Growth Factor beta1: genetics / Matrix
Metalloproteinase 11: metabolism / Matrix Metalloproteinase
11: genetics / Disease Progression / Cell Line, Tumor / Gene
Expression Regulation, Neoplastic / ALDH1A1 (Other) / Liquid
biopsy (Other) / MMP11 (Other) / Metastasis (Other) /
Prostate cancer (Other) / TGF-β1 (Other) / Aldehyde
Dehydrogenase 1 Family (NLM Chemicals) / Retinal
Dehydrogenase (NLM Chemicals) / Biomarkers, Tumor (NLM
Chemicals) / ALDH1A1 protein, human (NLM Chemicals) /
Transforming Growth Factor beta1 (NLM Chemicals) / Matrix
Metalloproteinase 11 (NLM Chemicals) / TGFB1 protein, human
(NLM Chemicals)},
cin = {DD01},
ddc = {610},
cid = {I:(DE-He78)DD01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40122809},
doi = {10.1186/s13046-025-03299-6},
url = {https://inrepo02.dkfz.de/record/300112},
}