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Expression of CRF1 and CRF2 Receptors in Human Cancers

Division of Cell Biology and Experimental Cancer Research (J.C.R., B.W.), Institute of Pathology, University of Berne, CH-3010 Berne, Switzerland; and The Clayton Foundation Laboratories for Peptide Biology (W.V., J.R.), The Salk Institute, La Jolla, California 92037-1099

Address all correspondence and requests for reprints to: Jean Claude Reubi, M.D., Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, P.O. Box 62, Murtenstrasse 31, CH-3010 Berne, Switzerland. E-mail: reubi{at}pathology.unibe.ch.

Overexpressed peptide receptors in human tumors represent clinically relevant targets for cancer diagnosis and therapy. Corticotropin-releasing factor (CRF) and its receptors have not been known to be involved in human cancer. The aim of the present study was to investigate such possibility by evaluating the expression of CRF₁ and CRF₂ receptors using in vitro autoradiography with subtype-selective CRF analogs in more than 200 primary human cancer samples. We show that a majority of pituitary adenomas express CRF receptors, often in high amounts. Whereas ACTH-producing adenomas preferentially express CRF₁ receptors, nonfunctioning adenomas (gonadotropin-producing and null-cell adenomas) and GH- and TSH-producing adenomas express CRF₂ receptors. Furthermore, several central and peripheral nervous system tumors express CRF receptors: medulloblastomas, paragangliomas, neuroblastomas, and some meningiomas express CRF₁ receptors, but ependymomas or Ewing sarcomas do not. Insulinomas can also express CRF receptors, whereas ductal pancreatic cancers or prostatic, colorectal, and non-small cell lung cancers lack CRF receptors. In all receptor-positive tumors, the receptors were located on tumor cells. The high incidence of CRF₁ or CRF₂ receptors in selected human tumors suggests that unlabeled CRF agonists may be evaluated as inhibitors of tumor cell proliferation in cancer therapy, and radiolabeled CRF analogs may be used for cancer diagnosis and/or radiotherapy.

This work was supported in part by NIH Grant DK26741.

Abbreviations: CRF, Corticotropin-releasing factor; GRP, gastrin-releasing peptide.

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