Targeting the sinusoidal-to-capillarized transition to normalize vessels in breast cancer liver metastasis

In human breast cancer liver metastases, metastasis-associated vessels arise from Lyve1+ LSECs and undergo a sinusoidal-to-capillarized transition, marked by inflammatory signaling, loss of sinusoidal markers, and gain of capillarized markers.

• Why it matters: Anti-VEGF and anti-angiogenic therapies fail in liver metastases, and the mechanisms behind this resistance are unclear, limiting effective vascular normalization strategies.
• What they did: The study combined single-cell RNA sequencing of human breast cancer liver metastases with a Lyve1+ LSEC lineage-tracing mouse model, then individually perturbed inflammatory and capillarization features, including Esm1.
• The result: Esm1 inhibition improved vessel perfusion and enhanced chemotherapeutic drug delivery, and Esm1 expression in tip cells correlated with poor patient prognosis, supporting Esm1 as a candidate target.

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