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000284364 1001_ $$aKomljenovic, Dorde$$b0
000284364 245__ $$aLocal metastatic expansion versus secondary intra-organ dissemination: two causes of neurological death explained by fundamentally different metastatic colonization patterns.
000284364 260__ $$aLondon$$bBiomed Central$$c2026
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000284364 520__ $$aNeurological failure contributes to 15-50% of deaths in patients with brain metastases, yet the underlying mechanisms remain poorly understood. Clinical causes range from local compression to meningeal metastasis. In this context, a link between infiltrative histopathological growth patterns (HGPs) and meningeal metastasis was recently described and prompted this reverse translation study.We conducted a retrospective postmortem histological assessment and a prospective MRI-based proof-of-concept study to explore neurological decline mechanisms in two experimental brain metastasis models with different HGPs: (i) the non-infiltrative TUBO model, characterized by well-defined tumor borders and a multilayered astrocytic capsule; and (ii) the infiltrative E0771-LG model, exhibiting diffuse infiltration and widespread astrogliosis.In the TUBO model, neurological death resulted from local metastatic expansion compressing vital structures, while the E0771-LG model caused mortality mainly through widespread secondary dissemination. We provide the first direct evidence of contralateral recolonization by secondary metastasis-initiating cells (secMICs), and highlight the high efficiency of secondary spread. Additionally, we show that secMICs exploit distinct anatomical structures to reach distant brain regions, bypassing classical vascular dissemination routes. Notably, the HGP and its associated features are intrinsic to tumor cells and are established early during metastatic colonization.This study identifies the HGP as a potential surrogate for predicting the underlying cause of organ failure in brain metastases. Additionally, it highlights the significant role of secondary dissemination and recolonization in brain metastasis, processes that have been largely overlooked in clinical practice. These findings address a critical knowledge gap and may inform future treatment strategies.
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000284364 650_7 $$2Other$$aBrain metastasis
000284364 650_7 $$2Other$$aCause of death
000284364 650_7 $$2Other$$aHistological growth pattern
000284364 650_7 $$2Other$$aInfiltration
000284364 650_7 $$2Other$$aLocal metastatic expansion
000284364 650_7 $$2Other$$aMMPI
000284364 650_7 $$2Other$$aMeningeal metastasis
000284364 650_7 $$2Other$$aNeurological decline
000284364 650_7 $$2Other$$aRecolonization
000284364 650_7 $$2Other$$aSecondary dissemination
000284364 650_2 $$2MeSH$$aBrain Neoplasms: secondary
000284364 650_2 $$2MeSH$$aBrain Neoplasms: pathology
000284364 650_2 $$2MeSH$$aBrain Neoplasms: diagnostic imaging
000284364 650_2 $$2MeSH$$aAnimals
000284364 650_2 $$2MeSH$$aHumans
000284364 650_2 $$2MeSH$$aMice
000284364 650_2 $$2MeSH$$aNeoplasm Metastasis
000284364 650_2 $$2MeSH$$aDisease Models, Animal
000284364 650_2 $$2MeSH$$aFemale
000284364 650_2 $$2MeSH$$aRetrospective Studies
000284364 650_2 $$2MeSH$$aMale
000284364 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000284364 650_2 $$2MeSH$$aNervous System Diseases: etiology
000284364 650_2 $$2MeSH$$aNervous System Diseases: pathology
000284364 7001_ $$aBäuerle, Tobias$$b1
000284364 7001_ $$aAlves-de-Lima, Jessica$$b2
000284364 7001_ $$aTrigueros, Laura$$b3
000284364 7001_ $$aDietz, Cara$$b4
000284364 7001_ $$aWinter, Zoltan$$b5
000284364 7001_ $$aAraceli, Tommaso$$b6
000284364 7001_ $$aStrotzer, Quirin$$b7
000284364 7001_ $$aWendl, Christina$$b8
000284364 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b9$$udzne
000284364 7001_ $$aProescholdt, Martin A$$b10
000284364 7001_ $$aHarter, Patrick N$$b11
000284364 7001_ $$aEvert, Katja$$b12
000284364 7001_ $$aPukrop, Tobias$$b13
000284364 7001_ $$00000-0002-4464-8189$$aBlazquez, Raquel$$b14
000284364 773__ $$0PERI:(DE-600)2091373-4$$a10.1186/s12943-026-02574-0$$gVol. 25, no. 1, p. 17$$n1$$p17$$tMolecular cancer$$v25$$x1476-4598$$y2026
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