FOLATE RECEPTOR OF HUMAN MAMMARY ADENOCARCINOMA

Binding of H-3-folate to human mammary tumor homogenate was of a high-affinity type (K=10(10) M(-1)) and displayed apparent positive cooperativity. Radioligand dissociation was slow at pH 7.4, but rapid at pH 3.5. As compared to methotrexate, 5-formyltetrahydrofolate acted as a strong inhibitor of radioligand binding. Gel chromatography of radioligand-labeled homogenate of tumor tissue revealed three peaks: a small greater than or equal to 110 kDa peak and two major peaks of folate-binding activity (M(r) similar to 25 kDa and M(r) similar to 100 kDa). Mammary tumor tissue showed immunostaining with rabbit antibodies against human milk folate binder. A parallel elevation in the concentrations of folate-binding protein and triglyceride in tumor tissue as compared to normal tissue adjacent to the tumor was compatible with the localization of folate-binding protein in the triglyceride-rich fraction of mammary gland homogenate.