ESCHERICHIA-COLI HEAT-STABLE ENTEROTOXIN RECEPTORS - A NOVEL MARKER FOR COLORECTAL TUMORS

PURPOSE: Receptors for Escherichia coil heat-stable toxin (ST) are sel ectively expressed in membranes of intestinal mucosa cells and colon c arcinoma cells in vitro, suggesting their use as a marker for colorect al tumors in vivo. The present studies examined the expression and fun ction of ST receptors in normal human tissues and primary and metastat ic colorectal tumors obtained from patients at surgery. METHODS: Surgi cal specimens were obtained as follows: from normal colon; from primar y adenocarcinomas from all anatomic divisions of the colon and rectum; from gallbladder, kidney, liver, lung, lymph node, ovary, peritoneum, stomach; and from colon carcinomas metastatic to liver, lung, lymph n ode, ovary, and peritoneum. Membranes prepared from these specimens we re assessed for the presence and functional characteristics of ST rece ptors. RESULTS: ST bound specifically to membranes from each division of normal colon and rectum and all primary and metastatic colorectal t umors examined. The affinity and density of ST receptors were similar in tumors of different grades and from various metastatic sites. ST-re ceptor interaction was coupled to activation of guanylyl cyclase in al l normal samples of colon and rectum and all primary and metastatic co lorectal tumors examined. In contrast, neither ST binding nor ST activ ation of guanylyl cyclase was detected in any extraintestinal tissues examined. CONCLUSIONS: Functional ST receptors are expressed in normal colonic tissue and primary and metastatic colorectal tumors but not b y extraintestinal tissues in humans. Expression of ST receptors does n ot vary as a function of the metastatic site or grade of these tumors. Receptors expressed by colorectal tumors retain their characteristic function, with binding of ST coupled to activation of guanylyl cyclase . These studies support the suggestion that ST receptors represent a s pecific marker for human colorectal tumors that may have use as a targ et for directing diagnostics and therapeutics to these tumors in vivo.