Shaping the Inflammatory Niche: Cancer-Associated Fibroblasts Facilitate Breast Cancer Metastasis

Mortality from breast cancer is almost exclusively a result of tumor metastasis. Formation of a hospitable microenvironment in the target distant organ is required for the establishment of metastases. Cancer-associated fibroblasts (CAFs) are prominent players in the microenvironment of many primary tumors, including breast cancer. However, the role of CAFs in the formation of a permissive metastatic niche is still largely unresolved. To characterize the co-evolution of CAFs during the formation of lung metastases, we isolated lung fibroblasts in an unbiased manner from normal mice, or from mice with micro- or macro-metastases and profiled their transcriptome by RNA-Seq. Data analysis revealed that fibroblasts in the lung metastatic niche are transcriptionally dynamic and plastic. Characterization of the most prominent transcriptional programs indicated that the main tasks operative in metastases-associated fibroblasts include extracellular matrix remodeling, stress response and shaping the immune milieu at the metastatic niche.