Bombesin receptor subtypes in human cancers: detection with the universal radioligand (125)I-[D-TYR(6), beta-ALA(11), PHE(13), NLE(14)] bombesin(6-14).
OBJECTIVE
Bombesin and bombesin receptors have been shown to play a role in cancer. Whereas the gastrin-releasing peptide (GRP) receptor is a bombesin receptor subtype frequently expressed by tumors, the other three subtypes, the neuromedin B (NMB), BB3, and BB4 receptors, have been poorly investigated in human tissues.


METHODS
We investigated 161 human tumors for their bombesin receptor subtype expression using in vitro receptor autoradiography with the universal bombesin radioligand (125)I-[D-Tyr(6), beta-Ala(11), Phe(13), Nle(14)]bombesin(6-14) in displacement experiments with unlabeled GRP, bombesin, NMB, and [D-Tyr(6), beta-Ala(11), Phe(13), Nle(14)]bombesin(6-14). The distinct rank order of potencies of these analogues for each receptor subtype allows us to identify the predominant subtype expressed by each tumor.


RESULTS
Twelve of 12 prostate cancers, 41 of 57 breast cancers, and 5 of 5 gastrinomas expressed predominantly GRP receptors; 11 of 24 intestinal, 1 of 26 bronchial, and 1 of 1 thymic carcinoids had preferentially NMB receptors; 9 of 26 bronchial carcinoids, 1 large cell neuroendocrine lung carcinoma, and 4 of 9 small cell lung carcinomas had preferentially BB3 receptors, whereas 3 of 9 small cell lung carcinomas had GRP receptors. Renal cell carcinomas had GRP receptors in 6 of 16 cases and BB3 receptors in 4 of 16 cases. Finally, 2 of 10 Ewing sarcomas had BB3 receptors. In situ hybridization detected BB3 receptor mRNA in neuroendocrine tumors expressing the BB3 protein.


CONCLUSIONS
This is the first study detecting the proteins of BB3, NMB, and GRP receptors in a group of human tumors using differential binding techniques. Particularly relevant is the BB3 expression in lung carcinoids and other neuroendocrine lung tumors, whereas gastrointestinal carcinoids preferably express NMB receptors. These tumors may be targets for diagnostic and radiotherapeutic applications of subtype-selective bombesin analogues.
Reubi
Jean Claude
JC
Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, CH-3010 Berne, Switzerland. reubi@patho.unibe.ch
Wenger
Sandra
S
Schmuckli-Maurer
Jacqueline
J
Schaer
Jean-Claude
JC
Gugger
Mathias
M
D001345:Autoradiography; D001667:Binding, Competitive; D001839:Bombesin / Q000031:analogs & derivatives / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001984:Bronchial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002276:Carcinoid Tumor / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007457:Iodine Radioisotopes; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011869:Radioligand Assay; D018004:Receptors, Bombesin / Q000235:genetics / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D007457:Iodine Radioisotopes; D018004:Receptors, Bombesin; C107120:bombesin receptor subtype 3; C107121:bombesin receptor subtype 4; D001839:Bombesin