Breast Cancer-Secreted Laminin γ2 Promotes Metastatic Progression Through Attraction of Blood Vessels

Tumor angiogenesis is one of the hallmarks of cancer and a critical step during the metastatic process. Here, we show that the extracellular matrix protein laminin γ2 is secreted by breast cancer cells and attracts endothelial cells to form new blood vessels at the metastatic site. The laminin γ2 chain acts as a pro-angiogenic factor, enhancing the migratory activity of endothelial cells via phosphorylation of VEGFR1. The newly established blood vessels accelerate metastatic growth and decrease survival in an orthotopic mouse model of breast cancer. Our study not only reveals a direct role of the laminin γ2 chain in tumor angiogenesis, but also identifies the laminin γ2 chain as a promising new target to abrogate metastatic growth in breast cancer patients. Moreover, our results suggest that angiogenesis is critical for early metastatic tumor formation, independent of tumor size and oxygenation.