The interaction of
estramustine and
estromustine, cytotoxic metabolites of
estramustine phosphate (
Estracyt), with protein-binding sites in rat pancreatic tissue was examined. These compounds were bound with relatively high affinity (Kd 10 nmol/L) to binding sites constituting 0.02-0.03% of total
protein. Further characterization of these binding sites revealed a native molecular weight of 24-30,000 a sedimentation coefficient of 3.4 S, and a heterogenous surface-charge distribution by ion-exchange chromatography. Removal of endogenously bound
ligand(s) by
acetone precipitation or
charcoal treatment increased binding significantly. Similar binding sites were present in two of two human pancreatic
tumors, but was low or absent in the only histopathologically normal pancreas examined as well as in serum and pancreatic juice. These binding sites were distinct from the "
estrogen-
binding protein" reported in normal pancreas from various species, but were similar to the "
estramustine-binding protein" (
EMBP) in rat ventral prostate with respect to
ligand specificity and the positive effect of endogenous
ligand removal on binding. Furthermore, specimens demonstrating presence of these binding sites also indicated cross-reactivity with
antibodies raised against the latter
protein, suggesting an immunochemical relation between estra-/
estromustine-binding sites in the pancreas and rat prostate
EMBP. The presence of high-affinity sites for
estramustine and
estromustine in human
pancreatic carcinomas make this type of
tumor a possible target tissue for compounds that exert antiproliferative as well as
antimitotic activity in vitro.