Fig. 8: Modelling BCLM by intracardiac or intracerebroventricular injection of PDOs.

BCLM PDOs were dissociated into single cells. a 0.5–1.0 × 10⁶ cells inoculated into the left cardiac ventricle under ultrasound guidance. Upper panel, IVIS imaging immediately after cell injection (day 0) and at endpoint for each mouse (development of significant morbidity), day 40–210. Middle panel, metastatic site involvement assessed by lamin A/C staining of FFPE sections. Bar charts show percentage of mice with disseminated tumour cells in individual organs, with pale bars indicating with single or small clusters of cells (1–10 cells) and dark bars indicating tissues with metastatic deposits ( > 10 cells), source data are provided as a Source Data file. Bottom panel. IHC staining for human lamin A/C of whole cranium and spine FFPE sections showing tumour cells growing along the meninges (orange arrowheads) or in the brain parenchyma (blue arrowheads), in the dura (red arrowheads) and pituitary (green arrowhead). Scale bars; Left, 100 µm; other panels, 1 mm. b 1 × 10⁵ cells inoculated intracerebroventricularly (ICV) (n = 4 mice). Left panel, IVIS imaging on day 0 and day 81 (endpoint) showing development of metastasis in two mice. Right panels, cranium and spine FFPE sections stained for human lamin A/C. Orange arrowheads indicate leptomeningeal involvement. Scale bars; 250 µm. Created with BioRender.com.