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Expression of CRF1 and CRF2 receptors in human cancers
Jean Claude Reubi1, Beatrice Waser, Wylie Vale
1Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, CH-3010 Berne, Switzerland. reubi@pathology.unibe.ch
Abstract:
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.
Insights
Corticotropin-releasing factor (CRF) receptors are found in many human tumors, including pituitary, nervous system, and insulinomas. This discovery suggests potential new diagnostic and therapeutic strategies for cancer using CRF-targeting agents.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Peptide receptors are frequently overexpressed in human tumors, serving as targets for diagnosis and therapy.
- The role of Corticotropin-releasing factor (CRF) and its receptors in human cancer has not been previously established.
Purpose of the Study:
- To investigate the expression of CRF receptor subtypes 1 and 2 in a large cohort of human cancer samples.
- To determine if CRF receptors are potential targets for novel cancer diagnostic and therapeutic interventions.
Main Methods:
- Utilized in vitro autoradiography with subtype-selective CRF analogs.
- Analyzed over 200 primary human cancer samples, including pituitary adenomas, nervous system tumors, and various other cancer types.
- Correlated receptor expression with specific tumor types and hormone production where applicable.
Main Results:
- A majority of pituitary adenomas expressed CRF receptors, with ACTH-producing adenomas showing a preference for CRF(1) receptors, and nonfunctioning/GH/TSH-producing adenomas expressing CRF(2) receptors.
- CRF receptors were detected in medulloblastomas, paragangliomas, neuroblastomas, meningiomas, and insulinomas, but not in ependymomas, Ewing sarcomas, ductal pancreatic cancers, or prostate, colorectal, and non-small cell lung cancers.
- Receptors were consistently located on the tumor cells in all positive samples.
Conclusions:
- The significant incidence of CRF(1) and CRF(2) receptors in specific human tumors highlights their potential as therapeutic targets.
- Unlabeled CRF agonists could be explored for inhibiting tumor cell proliferation.
- Radiolabeled CRF analogs may offer new avenues for cancer diagnosis and radiotherapy.