Figure 2.
Breast cancer brain metastases overexpress LAT1 both in patient samples and in an in vivo mouse model. A–D, Patient samples of breast cancer brain metastases show higher LAT1 levels compared with normal brain. A, TNBC brain metastasis displays characteristic membrane staining of LAT1. B, LAT1 signal in normal brain tissue is associated with blood vessels. C and D, Representative images of LAT1 staining in TNBC brain metastases with adjacent normal brain; scale bars, 200 μmol/L (A–C), 400 μmol/L (D). E and F, Representative images of LAT1 staining in mouse brain metastases formed after ICA injection of TNBC cells. E, Brain metastases formed after ICA injection of MDA-MB-231-BR3 cells. Left, bulky metastasis located in the brain parenchyma (arrowhead) and in the meninges (arrows). Right, Metastatic spread in the meninges. H&E staining shows MDA-MB-231-BR3 tumor cells in the leptomeningeal space between the brain and the skull. Arrows point to metastases; scale bar, 1,000 μmol/L. Inset, Empty space between metastasis and the brain is due to a common artefact of whole-skull fixation. F, Leptomeningeal metastases formed after ICA injection of HCC1806 cells; scale bar, 400 μmol/L. G, LAT1 expression in metastases formed after ICA injection of MDA-MB-231-BR3 is higher than in normal brain; scale bars left to right, 200, 400, and 200 μmol/L. Right, Average LAT1 antibody fluorescence intensity quantification based on 3–4 metastases (10–30 fields per metastasis and adjacent brain) from n = 3 mice. Data are mean ± SD. ****, P < 0.0001; NB, normal brain.
