Tumor cell JAGGED1 promotes lymph node metastasis and predicts recurrence in lymph node positive breast cancer patients

Tumor cell invasion of lymph nodes facilitates breast cancer progression. The adverse impact of lymph node metastasis necessitates biomarker identification to predict outcomes and guide treatment. We established the Notch ligand, JAG1, as a driver of lymph node metastasis. Tumor microarray analysis of synchronous breast tumor and lymph node samples from 380 patients demonstrated that tumor cells metastasized to the lymph nodes show higher JAG1 expression than matched primary tumors. In mouse models, JAG1 expression in tumor cells increased the frequency of tumor lymphovascular invasion and the level of lymph node metastasis. Patients with low JAG1 in lymph node metastatic cells showed significantly increased 5-year recurrence free survival rates compared to patients with high lymph node JAG1. We conclude that JAG1 expression promotes lymphogenous metastasis and provides one of the first predictive clinical biomarkers derived from patient lymph node tissue staining.