EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN BREAST-CANCER CORRELATES WITH METASTATIC DISEASE

Breast cancer is characterized by its ability to metastasize rapidly. Factors that might facilitate this metastatic potential include tumor vascularity. Nitric oxide (NO), a labile compound synthesized by NO sy nthase (NOS), is a major regulator not only of physiologic vascular to ne but also of the abnormal vascularity associated with many tumors. T o test whether NOS is expressed in primary breast tumors and whether i ts expression is associated with the presence of metastasis, we analyz ed the expression of the inducible NOS in 22 primary breast tumors, an d to investigate its association to other gene products related to the metastatic ability of tumor cells, we correlated the expression of th e inducible NOS with the expression of the nm23 protein (the product o f the putative antimetastatic gene nm23). We found a very strong corre lation between the presence of NOS and axillary lymph node metastasis and between NOS and the absence of nm23 protein These data suggest tha t NO synthesis and the resulting increase in blood now to the tumor pl ay a role in the facilitation of tumor metastasis.