THE HIGH-AFFINITY FOLATE RECEPTOR OF NORMAL AND MALIGNANT HUMAN COLONIC MUCOSA

The hypothesis that folate depletion is a risk factor for development of colonic neoplasia prompted us to study the presence of a putative f olate receptor in human colon mucosa. Binding of H-3-folate to normal and malignant mucosa studied by equilibrium dialysis was of a high-aff inity type (K = 10(10) L/mol) and displayed apparent positive cooperat ivity. Radioligand dissociation was slow at pH 7.4, but rapid at pH 3. 5. As compared to methotrexate, 5-formyltetrahydrofolate was a potent inhibitor of binding. Gel filtration revealed a 25 kDa and 100 kDa pea k of folate-binding activity. Immunoreactivity studies were performed with rabbit antibodies against human 25 kDa milk folate-binding protei n. Immunoblotting showed a single band at 65 kDa, and tissue sections exhibited immunostaining of mucosal areas. The present folate receptor with characteristics similar to those of other high-affinity folate-b inding proteins may serve as a regulator of intracellular folate conce ntration in colon mucosa.