Initiation of breast cancer metastasis in the brain depends on tumor architectures and microenvironment
The researchers reveal distinct tumor architectures, stromal interfaces, and tumor-intrinsic mechanisms that are preferentially adopted by prevalent brain metastases during the initiation of colonization.
The authors show that TNBC mouse models tend to form perivascular sheaths with diffusive contact with astrocytes and microglia. In contrast, HER2BC models tend to form compact spheroids driven by autonomous tenascin C production, segregating stromal cells to the periphery.
Single-cell transcriptomics also reveal differential Alzheimer’s disease-associated microglia (DAM) responses and engagement of the GAS6 receptor AXL.
These findings highlight critical spatial and microenvironmental features that can be leveraged to target minimal residual disease in the brain.
https://www.cell.com/cancer-cell/fulltext/S1535-6108(24)00314-3
