Expression of the Calcitonin Receptor-like Receptor (CALCRL) in Normal and Neoplastic Tissues

• Published in: International journal of molecular sciences Vol. 24; no. 4; p. 3960
• Main Authors: Wende, Benjamin, Beyer, Anna-Sophia Liselott, Ruhnke, Niklas, Kaemmerer, Daniel, Sänger, Jörg, Schulz, Stefan, Lupp, Amelie
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: adrenomedullin; Adrenomedullin - metabolism; adrenomedullin receptor; amylin; Analysis; Animals; Antibodies; Antimitotic agents; Antineoplastic agents; Arteries; Arteries - metabolism; Arterioles; Bronchi; Bronchus; Calcitonin; calcitonin gene-related peptide; calcitonin gene-related peptide receptor; Calcitonin Receptor-Like Protein - metabolism; calcitonin receptor-like receptor; Capillaries; Cerebral cortex; Diabetes; Dorsal root ganglia; Endothelium; Experiments; Humans; Immune system; Immunocytochemistry; Intestinal Mucosa - metabolism; Intestine; Intestines - metabolism; Labeling; Leydig cells; Lung cancer; Lung carcinoma; Lungs; Lymphoma; Male; Mice; Monoclonal antibodies; Muscles; Neoplasms; Neoplasms - metabolism; Neuroendocrine tumors; Osteoporosis; Pancreas; Pancreatic carcinoma; Parathyroid; Peptides; Pituitary; Pituitary gland; Pramlintide; Proteins; Rats; Renal cell carcinoma; Scientific equipment and supplies industry; siRNA; Small intestine; Thyroid carcinoma; Tumors; Type 2 diabetes; United States; Germany; amylin receptor; calcitonin gene-related peptide receptor; adrenomedullin; antibody; calcitonin receptor-like receptor; receptor activity-modifying protein; calcitonin gene-related peptide; amylin; immunohistochemistry; adrenomedullin receptor; tumours
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24043960

Little information is available concerning protein expression of the calcitonin receptor-like receptor (CALCRL) at the protein level. Here, we developed a rabbit monoclonal antibody, 8H9L8, which is directed against human CALCRL but cross-reacts with the rat and mouse forms of the receptor. We confirmed antibody specificity via Western blot analyses and immunocytochemistry using the CALCRL-expressing neuroendocrine tumour cell line BON-1 and a CALCRL-specific small interfering RNA (siRNA). We then used the antibody for immunohistochemical analyses of various formalin-fixed, paraffin-embedded specimens of normal and neoplastic tissues. In nearly all tissue specimens examined, CALCRL expression was detected in the capillary endothelium, smooth muscles of the arterioles and arteries, and immune cells. Analyses of normal human, rat, and mouse tissues revealed that CALCRL was primarily present in distinct cell populations in the cerebral cortex; pituitary; dorsal root ganglia; epithelia, muscles, and glands of the larger bronchi; intestinal mucosa (particularly in enteroendocrine cells); intestinal ganglia; exocrine and endocrine pancreas; arteries, capillaries, and glomerular capillary loops in the kidneys; the adrenals; Leydig cells in the testicles; and syncytiotrophoblasts in the placenta. In the neoplastic tissues, CALCRL was predominantly expressed in thyroid carcinomas, parathyroid adenomas, small-cell lung cancers, large-cell neuroendocrine carcinomas of the lung, pancreatic neuroendocrine neoplasms, renal clear-cell carcinomas, pheochromocytomas, lymphomas, and melanomas. In these tumours with strong expression of CALCRL, the receptor may represent a useful target structure for future therapies.