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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 CRF(1) and CRF(2) 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 CRF(1) receptors, nonfunctioning adenomas (gonadotropin-producing and null-cell adenomas) and GH- and TSH-producing adenomas express CRF(2) receptors. Furthermore, several central and peripheral nervous system tumors express CRF receptors: medulloblastomas, paragangliomas, neuroblastomas, and some meningiomas express CRF(1) 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 CRF(1) or CRF(2) 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.

Expression of CRF1 and CRF2 Receptors in Human Cancers