Gastrointestinal
peptide hormone receptors, like
somatostatin receptors, are often overexpressed in human
cancer, allowing receptor-targeted
tumor imaging and
therapy. A novel candidate for these applications is the
secretin receptor recently identified in pancreatic and
cholangiocellular carcinomas. In the present study,
secretin receptors were assessed in a non-gastrointestinal tissue, the human lung. Non-small-cell
lung cancers (n=26), small-cell
lung cancers (n=10), bronchopulmonary
carcinoid tumors (n=29), and non-neoplastic lung (n=46) were investigated for
secretin receptor protein expression with in vitro receptor autoradiography, using (125)I-[Tyr(10)] rat
secretin and for
secretin receptor transcripts with RT-PCR.
Secretin receptor protein expression was found in 62% of bronchopulmonary
carcinoids in moderate to high density, in 12% of non-small cell
lung cancers in low density, but not in small cell
lung cancers. In
tumors found to be
secretin receptor positive by autoradiography, RT-PCR revealed transcripts for the wild-type
secretin receptor and for novel
secretin receptor splice variants. In the non-neoplastic lung,
secretin receptor protein expression was observed in low density along the alveolar septa in direct
tumor vicinity in cases of acute
inflammation, but not in histologically normal lung. In the autoradiographically positive peritumoral lung, RT-PCR showed transcripts for the wild-type
secretin receptor and for a
secretin receptor spliceoform different from those occurring in lung and gut
tumors. In conclusion,
secretin receptors are new markers for bronchopulmonary
carcinoid tumors, and represent the molecular basis for an in vivo targeting of
carcinoid tumors for diagnosis and
therapy. Furthermore,
secretin receptors may play a role in peritumoral lung pathophysiology.
Secretin receptor mis-splicing specifically occurs in
tumor and non-
tumor lung pathology.