Wild-type and splice-variant secretin receptors in lung cancer: overexpression in carcinoid tumors and peritumoral lung tissue

Körner, Meike U; Hayes, Gregory M; Carrigan, Patricia E; Rehmann, Ruth; Miller, Laurence J; Reubi, Jean C (2008). Wild-type and splice-variant secretin receptors in lung cancer: overexpression in carcinoid tumors and peritumoral lung tissue. Modern pathology, 21(4), pp. 387-95. London: Nature Publishing Group 10.1038/modpathol.3801005

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Körner Jachertz, Meike; Rehmann, Ruth and Reubi-Kattenbusch, Jean-Claude

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0893-3952

ISBN:

18223557

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:02

Last Modified:

15 Oct 2019 12:43

Publisher DOI:

10.1038/modpathol.3801005

PubMed ID:

18223557

Web of Science ID:

000254288500004

URI:

https://boris.unibe.ch/id/eprint/27068 (FactScience: 101633)

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