C-cells etiology and calcitonin/cgrp family of peptides. Literature review
https://doi.org/10.14341/ket12805
Abstract
Medullary thyroid cancer (MTC) is a rare form of cancer derived from parafollicular or C cells. Currently, there is an active search for predictors of the course of MTC and markers that can predict the treatment response. Understanding the biological characteristics of the tumor requires insights from both embryology and genetics. While the genetic aspects of MTC are relatively well-studied, the embryonic origin of C-cells remains a subject of ongoing investigation. The prevailing hypothesis suggests an ectodermal origin, yet recent studies have identified the expression of markers in C-cells that are typical of cells with endodermal lineage. These data deepen the understanding of their biological role and provide reasons for further research. C-cells produce several essential hormones, including calcitonin, and possess a unique ability to synthesize and secrete other peptide hormones. This article focuses on members of the calcitonin family of hormones — calcitonin gene-related peptide, amylin, adrenomedullin, and intermedin — which regulate critical physiological processes. Some of these hormones and their receptors have been identified in malignant tumors and are associated with poorer prognosis. This review analyzes current findings on the origins of C-cells and calcitonin precursors, along with structurally similar peptides, highlighting their importance in the context of clinical oncology.
About the Authors
A. Chevais
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Anastassia Chevais, MD, PhD
11 Dm. Ulyanova street, 117292, Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
E. V. Bondarenko
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Ekaterina V. Bondarenko, MD, PhD
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
K. Yu. Slashchuk
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Konstantin Yu. Slashchuk, MD, PhD
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
A. K. Ebzeeva
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Aminat K. Ebzeeva, MD
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
K. D. Vikhireva
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Competing Interests:
Russian Federation
Ksenya D. Vikhireva, student
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
D. G. Beltsevich
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Dmitry G. Beltsevich, MD, PhD
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
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Supplementary files
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1. Figure 1: Calcitonin biosynthesis and calcitonin gene-associated peptide on the matrix of the CALC I gene (adapted from Russel F et al. (2014)). The CALC I gene contains six exons: exons I-IV comprise the mRNA of the calcitonin precursor, preprocalcitonin, while preproCGRP is encoded by exons I-III and V-IV. Alternative splicing of CALC I mRNA is tissue-specific: calcitonin mRNA is produced mainly in thyroid C-cells, whereas CGRPα mRNA is produced in the nervous system. CGRPα — calcitonin gene-associated peptide; CT — calcitonin. Image created in Biorender.com software. | |
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2. Figure 2: Biosynthesis of calcitonin gene-associated peptide β (CGRPβ) on the CALC II gene matrix. CGRPβ — calcitonin gene-associated peptide; CT — calcitonin. Image created in Biorender.com software. | |
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3. Figure 3: Calcitonin family receptors, ligands and their affinity. Ligands (peptide hormones) are indicated by spheres (proximity to the receptor demonstrates their relative potency - the closer to the receptor binding site, the greater the affinity). ADM — adrenomedullin; AD1MR — adrenomedullin-1 receptor; AD1MR — adrenomedullin-2 (intermedin) receptor; AM — amylin; AM1R — amylin-1 receptor; AM2R — amylin-2 receptor; AM3R — amylin-3 receptor; CGRP — calcitonin gene-related peptide; CGRPR — calcitonin gene-related peptide receptor; CLR, — calcitonin receptor-like receptor; CT, — calcitonin; CTR — calcitonin receptor; Gα — alpha subunit of G-protein; RAMP1, 2, 3 — transmembrane proteins belonging to the RAMP family of type 1, 2, 3; RCP — receptor coupling protein. The image was created in Biorender.com software. | |
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Review
For citations:
Chevais A., Bondarenko E.V., Slashchuk K.Yu., Ebzeeva A.K., Vikhireva K.D., Beltsevich D.G. C-cells etiology and calcitonin/cgrp family of peptides. Literature review. Clinical and experimental thyroidology. 2024;20(3):4-13. (In Russ.) https://doi.org/10.14341/ket12805
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