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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},
}