% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Komljenovic:284364,
      author       = {Komljenovic, Dorde and Bäuerle, Tobias and Alves-de-Lima,
                      Jessica and Trigueros, Laura and Dietz, Cara and Winter,
                      Zoltan and Araceli, Tommaso and Strotzer, Quirin and Wendl,
                      Christina and Brendel, Matthias and Proescholdt, Martin A
                      and Harter, Patrick N and Evert, Katja and Pukrop, Tobias
                      and Blazquez, Raquel},
      title        = {{L}ocal metastatic expansion versus secondary intra-organ
                      dissemination: two causes of neurological death explained by
                      fundamentally different metastatic colonization patterns.},
      journal      = {Molecular cancer},
      volume       = {25},
      number       = {1},
      issn         = {1476-4598},
      address      = {London},
      publisher    = {Biomed Central},
      reportid     = {DZNE-2026-00132},
      pages        = {17},
      year         = {2026},
      abstract     = {Neurological failure contributes to $15-50\%$ of deaths in
                      patients with brain metastases, yet the underlying
                      mechanisms remain poorly understood. Clinical causes range
                      from local compression to meningeal metastasis. In this
                      context, a link between infiltrative histopathological
                      growth patterns (HGPs) and meningeal metastasis was recently
                      described and prompted this reverse translation study.We
                      conducted a retrospective postmortem histological assessment
                      and a prospective MRI-based proof-of-concept study to
                      explore neurological decline mechanisms in two experimental
                      brain metastasis models with different HGPs: (i) the
                      non-infiltrative TUBO model, characterized by well-defined
                      tumor borders and a multilayered astrocytic capsule; and
                      (ii) the infiltrative E0771-LG model, exhibiting diffuse
                      infiltration and widespread astrogliosis.In the TUBO model,
                      neurological death resulted from local metastatic expansion
                      compressing vital structures, while the E0771-LG model
                      caused mortality mainly through widespread secondary
                      dissemination. We provide the first direct evidence of
                      contralateral recolonization by secondary
                      metastasis-initiating cells (secMICs), and highlight the
                      high efficiency of secondary spread. Additionally, we show
                      that secMICs exploit distinct anatomical structures to reach
                      distant brain regions, bypassing classical vascular
                      dissemination routes. Notably, the HGP and its associated
                      features are intrinsic to tumor cells and are established
                      early during metastatic colonization.This study identifies
                      the HGP as a potential surrogate for predicting the
                      underlying cause of organ failure in brain metastases.
                      Additionally, it highlights the significant role of
                      secondary dissemination and recolonization in brain
                      metastasis, processes that have been largely overlooked in
                      clinical practice. These findings address a critical
                      knowledge gap and may inform future treatment strategies.},
      keywords     = {Brain Neoplasms: secondary / Brain Neoplasms: pathology /
                      Brain Neoplasms: diagnostic imaging / Animals / Humans /
                      Mice / Neoplasm Metastasis / Disease Models, Animal / Female
                      / Retrospective Studies / Male / Magnetic Resonance Imaging
                      / Nervous System Diseases: etiology / Nervous System
                      Diseases: pathology / Brain metastasis (Other) / Cause of
                      death (Other) / Histological growth pattern (Other) /
                      Infiltration (Other) / Local metastatic expansion (Other) /
                      MMPI (Other) / Meningeal metastasis (Other) / Neurological
                      decline (Other) / Recolonization (Other) / Secondary
                      dissemination (Other)},
      cin          = {AG Haass},
      ddc          = {570},
      cid          = {I:(DE-2719)1110007},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41580751},
      pmc          = {pmc:PMC12849154},
      doi          = {10.1186/s12943-026-02574-0},
      url          = {https://pub.dzne.de/record/284364},
}