Escherichia coli heat-stable toxin receptors in human colonic tumors.
OBJECTIVE
Escherichia coli heat-stable enterotoxins (ST) are small peptides of 18 or 19 amino acids that bind to specific cell surface receptors located on the intestinal brush border and activate guanylate cyclase, resulting in an increase in the intracellular cyclic guanosine 3',5'-monophosphate content of the cell. The present study examined whether receptors for ST are expressed by primary and metastatic human colonic tumors in vivo.


METHODS
Plasma membranes prepared from surgical tissue samples from normal colon, liver and lung, primary colonic adenocarcinomas, and colon carcinomas metastatic to lung and liver were analyzed for the structural and functional characteristics of constituent ST receptors.


RESULTS
All primary and metastatic colonic tumors examined bound ST, showing receptors of high (pmol/L) and low (nmol/L) affinity with densities that were similar to those in normal colon. Also, affinity cross-linking of labeled ST to membranes showed similar binding proteins in primary and metastatic tumors and normal colon. ST binding and affinity-labeled proteins were not detected in normal extraintestinal tissues. Guanylate cyclase was activated by ST in membranes from all colonic tumors studied, with efficacies and potencies that were similar to those in normal colon. ST did not activate this enzyme in normal extraintestinal tissues.


CONCLUSIONS
Receptors for ST are expressed by primary and metastatic human colonic tumors in vivo, with structural and functional characteristics that are similar to those in normal human colon.
Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania.
S L
SL
Carrithers
S J
SJ
Parkinson
S
S
Goldstein
P
P
Park
D C
DC
Robertson
S A
SA
Waldman
D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism / Q000556:secondary; D001427:Bacterial Toxins / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D003106:Colon / Q000201:enzymology / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004768:Enterotoxins / Q000378:metabolism*; D004789:Enzyme Activation; D029968:Escherichia coli Proteins; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000556:secondary; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000378:metabolism
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D018000:Receptors, Peptide; C034151:heat stable toxin (E coli); D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled