PURPOSE: Receptors for Escherichia coli heat-stable toxin (ST) are selectively expressed in membranes of intestinal mucosa cells and colon carcinoma cells in vitro, suggesting their use as a marker for colorectal tumors in vivo. The present studies examined the expression and function of ST receptors in normal human tissues and primary and metastatic colorectal tumors obtained from patients at surgery. METHODS: Surgical specimens were obtained as follows: from normal colon; from primary 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 node, ovary, and peritoneum. Membranes prepared from these specimens were assessed for the presence and functional characteristics of ST receptors. RESULTS: ST bound specifically to membranes from each division of normal colon and rectum and all primary and metastatic colorectal tumors examined. The affinity and density of ST receptors were similar in tumors of different grades and from various metastatic sites. ST-receptor interaction was coupled to activation of guanylyl cyclase in all normal samples of colon and rectum and all primary and metastatic colorectal tumors examined. In contrast, neither ST binding nor ST activation 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 by extraintestinal tissues in humans. Expression of ST receptors does not 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 specific marker for human colorectal tumors that may have use as a target for directing diagnostics and therapeutics to these tumors in vivo.
PURPOSE: Receptors for Escherichia coli heat-stable toxin (ST) are selectively expressed in membranes of intestinal mucosa cells and colon carcinoma cells in vitro, suggesting their use as a marker for colorectal tumors in vivo. The present studies examined the expression and function of ST receptors in normal human tissues and primary and metastatic colorectal tumors obtained from patients at surgery. METHODS: Surgical specimens were obtained as follows: from normal colon; from primary 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 node, ovary, and peritoneum. Membranes prepared from these specimens were assessed for the presence and functional characteristics of ST receptors. RESULTS: ST bound specifically to membranes from each division of normal colon and rectum and all primary and metastatic colorectal tumors examined. The affinity and density of ST receptors were similar in tumors of different grades and from various metastatic sites. ST-receptor interaction was coupled to activation of guanylyl cyclase in all normal samples of colon and rectum and all primary and metastatic colorectal tumors examined. In contrast, neither ST binding nor ST activation 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 by extraintestinal tissues in humans. Expression of ST receptors does not 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 specific marker for humancolorectal tumors that may have use as a target for directing diagnostics and therapeutics to these tumors in vivo.
Authors: David L Garbers; Ted D Chrisman; Phi Wiegn; Takeshi Katafuchi; Joseph P Albanesi; Vincent Bielinski; Barbara Barylko; Margaret M Redfield; John C Burnett Journal: Trends Endocrinol Metab Date: 2006-06-30 Impact factor: 12.015
Authors: Khaldoun Almhanna; Maria Luisa Limon Miron; David Wright; Antonio Cubillo Gracian; Richard A Hubner; Jean-Luc Van Laethem; Carolina Muriel López; Maria Alsina; Frederico Longo Muñoz; Johanna Bendell; Irfan Firdaus; Wells Messersmith; Zhan Ye; Adedigbo A Fasanmade; Hadi Danaee; Thea Kalebic Journal: Invest New Drugs Date: 2017-02-11 Impact factor: 3.850
Authors: S L Carrithers; M T Barber; S Biswas; S J Parkinson; P K Park; S D Goldstein; S A Waldman Journal: Proc Natl Acad Sci U S A Date: 1996-12-10 Impact factor: 11.205
Authors: Khaldoun Almhanna; David Wright; Teresa Macarulla Mercade; Jean-Luc Van Laethem; Antonio Cubillo Gracian; Carmen Guillen-Ponce; Jason Faris; Carolina Muriel Lopez; Richard A Hubner; Johanna Bendell; Alain Bols; Jaime Feliu; Naureen Starling; Peter Enzinger; Devalingham Mahalingham; Wells Messersmith; Huyuan Yang; Adedigbo Fasanmade; Hadi Danaee; Thea Kalebic Journal: Invest New Drugs Date: 2017-05-19 Impact factor: 3.850
Authors: Adam E Snook; Benjamin J Stafford; Peng Li; Gene Tan; Lan Huang; Ruth Birbe; Stephanie Schulz; Matthias J Schnell; Mathew Thakur; Jay L Rothstein; Laurence C Eisenlohr; Scott A Waldman Journal: J Natl Cancer Inst Date: 2008-06-24 Impact factor: 13.506
Authors: J M Pearlman; S P Prawer; M T Barber; S J Parkinson; S Schulz; J Park; M Zook; S A Waldman Journal: Dig Dis Sci Date: 2000-02 Impact factor: 3.199