Butyrate induced reduction of tumor cell laminin receptors

Laminin, a glycoprotein of basement membranes, binds to the surface of cultured human pancreatic carcinoma cells (PANC-1). The binding is saturable, with a high proportion of specific binding, as determined by competition of labeled ligand with 80-fold excess unlabeled ligand. Pretreatment of the carcinoma cells with butyrate markedly reduces the amount of specific laminin binding. The butyrate effect on laminin binding is dose dependent and is observed at a concentration of butyrate which does not significantly reduce cellular protein synthesis or increase laminin production. Scatchard analysis indicates that butyrate reduces the total number of laminin binding sites without affecting the binding coefficient (Kd = 2 nm). The laminin receptor protein isolated from the PANC-1 cell extract has a molecular weight of approximately 70,000. After butyrate treatment the total amount of extractable laminin receptor protein is significantly reduced. Thus butyrate reduces laminin binding to PANC-1 carcinoma cells by a mechanism which involves decreased expression of laminin receptor proteins in the plasma membrane.