Natural cytotoxicity triggering receptor 3 is differentially expressed in lymph node metastasis in human breast cancer.
Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that natural cytotoxicity triggering receptor 3, NCR3, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that NCR3 was also differentially expressed in brain metastatic tissues. NCR3 mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of NCR3 in primary tumors of the breast was significantly correlated with patient overall survival, in lymph node negative patients but not in lymph node positive patients. Modulation of NCR3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.