Abstract
Human chromogranin A (CgA), a 439-residue long neurosecretory protein, can serve as a circulating biomarker for a wide range of neuroendocrine tumors. Increased levels of immunoreactive CgA are also present in the blood of patients with cardiovascular, gastrointestinal, or inflammatory diseases with, in certain cases, important diagnostic and prognostic implications. A growing body of evidence suggest that CgA and various CgA-derived fragments have complex roles in the regulation of cardiovascular system, metabolism, innate immunity, angiogenesis, and tissue repair, sometime with opposite biological effects. For example, while full-length CgA (CgA1-439) inhibits angiogenesis, the CgA1-373 fragment, at certain doses, is proangiogenic. Thus, the selective quantification of CgA and its fragments in the blood of patients (and in other biological fluids) is of great experimental and clinical interest. Here, we describe methods to produce CgA1-439 and CgA1-373 and to develop ELISAs capable of detecting these polypeptides in a very selective manner. The same approach can be used, in principle, also for developing assays for other fragments.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Banks P, Helle KB (1965) The release of protein from the stimulated adrenal medulla. Biochem J 97:40C–41C
Deftos LJ (1991) Chromogranin A: its role in endocrine function and as an endocrine and neuroendocrine tumor marker. Endocr Rev 12(2):181–187
Janson ET, Holmberg L, Stridsberg M, Eriksson B, Theodorsson E, Wilander E, Oberg K (1997) Carcinoid tumors: analysis of prognostic factors and survival in 301 patients from a referral center. Ann Oncol 8(7):685–690
Taupenot L, Harper KL, O’Connor DT (2003) The chromogranin-secretogranin family. N Engl J Med 348(12):1134–1149
Helle KB, Corti A, Metz-Boutigue MH, Tota B (2007) The endocrine role for chromogranin A: a prohormone for peptides with regulatory properties. Cell Mol Life Sci 64(22):2863–2886. https://doi.org/10.1007/s00018-007-7254-0
Portela-Gomes GM, Grimelius L, Wilander E, Stridsberg M (2010) Granins and granin-related peptides in neuroendocrine tumours. Regul Pept 165(1):12–20
Gadroy P, Stridsberg M, Capon C, Michalski JC, Strub JM, Van Dorsselaer A, Aunis D, Metz-Boutigue MH (1998) Phosphorylation and O-glycosylation sites of human chromogranin A (CGA79-439) from urine of patients with carcinoid tumors. J Biol Chem 273(51):34087–34097
Sanduleanu S, De Bruine A, Stridsberg M, Jonkers D, Biemond I, Hameeteman W, Lundqvist G, Stockbrugger RW (2001) Serum chromogranin A as a screening test for gastric enterochromaffin-like cell hyperplasia during acid-suppressive therapy. Eur J Clin Investig 31(9):802–811
Bianco M, Gasparri AM, Colombo B, Curnis F, Girlanda S, Ponzoni M, Bertilaccio MT, Calcinotto A, Sacchi A, Ferrero E, Ferrarini M, Chesi M, Bergsagel PL, Bellone M, Tonon G, Ciceri F, Marcatti M, Caligaris Cappio F, Corti A (2016) Chromogranin A is preferentially cleaved into pro-angiogenic peptides in the bone marrow of multiple myeloma patients. Cancer Res 76:1781–1179. https://doi.org/10.1158/0008-5472.CAN-15-1637
O’Connor DT, Bernstein KN (1984) Radioimmunoassay of chromogranin A in plasma as a measure of exocytotic sympathoadrenal activity in normal subjects and patients with pheochromocytoma. N Engl J Med 311(12):764–770
Loh YP, Cheng Y, Mahata SK, Corti A, Tota B (2012) Chromogranin A and derived peptides in health and disease. J Mol Neurosci 48(2):347–356. https://doi.org/10.1007/s12031-012-9728-2
Mahata SK, Corti A (2019) Chromogranin A and its fragments in cardiovascular, immunometabolic, and cancer regulation. Ann N Y Acad Sci 1455(1):34–58. https://doi.org/10.1111/nyas.14249
Crippa L, Bianco M, Colombo B, Gasparri AM, Ferrero E, Loh YP, Curnis F, Corti A (2013) A new chromogranin A-dependent angiogenic switch activated by thrombin. Blood 121(2):392–402. https://doi.org/10.1182/blood-2012-05-430314
Theurl M, Schgoer W, Albrecht K, Jeschke J, Egger M, Beer AG, Vasiljevic D, Rong S, Wolf AM, Bahlmann FH, Patsch JR, Wolf D, Schratzberger P, Mahata SK, Kirchmair R (2010) The neuropeptide catestatin acts as a novel angiogenic cytokine via a basic fibroblast growth factor-dependent mechanism. Circ Res 107(11):1326–1335. https://doi.org/10.1161/CIRCRESAHA.110.219493
Dallatomasina A, Gasparri AM, Colombo B, Sacchi A, Bianco M, Daniele T, Esposito A, Pastorino F, Ponzoni M, Marcucci F, Curnis F, Corti A (2019) Spatiotemporal regulation of tumor angiogenesis by circulating chromogranin A cleavage and neuropilin-1 engagement. Cancer Res 79(8):1925–1937. https://doi.org/10.1158/0008-5472.CAN-18-0289
Reni M, Andreasi V, Gasparri AM, Dugnani E, Colombo B, Macchini M, Bianco M, Dallatomasina A, Citro A, Assi E, Protti MP, Esposito A, Falconi M, Curnis F, Piemonti L, Corti A (2020) Circulating chromogranin A is cleaved into vasoregulatory fragments in patients with pancreatic ductal adenocarcinoma. Front Oncol 10:613582. https://doi.org/10.3389/fonc.2020.613582
Sambrook J, Fritsch EF, Maniatis T (eds) (1989) Molecular cloning a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Corti A, Longhi R, Gasparri A, Chen F, Pelagi M, Siccardi AG (1996) Antigenic regions of human chromogranin A and their topographic relationships with structural/functional domains. Eur J Biochem 235(1–2):275–280
Acknowledgments
The research leading to these results has received funding from AIRC under IG 2019 – ID. 23470 project – P.I. Corti Angelo.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Curnis, F., Colombo, B., Corti, A. (2023). Quantification of Chromogranin A and Its Fragments in Biological Fluids. In: Borges, R. (eds) Chromaffin Cells. Methods in Molecular Biology, vol 2565. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2671-9_23
Download citation
DOI: https://doi.org/10.1007/978-1-0716-2671-9_23
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-2670-2
Online ISBN: 978-1-0716-2671-9
eBook Packages: Springer Protocols