Chromogranin A in Physiology and Oncology ( chromogranin / neuroendocrine tumours / cleavage fragments / extracellular functions / intracellular functions / tumour marker )

Chromogranin A (CgA) is a hydrophilic acidic one-chain peptide containing 439 amino acids, preceded by NH 2 -terminal 18-amino-acid signal peptide; the complete pre-chromogranin A molecule thus encompasses 457 amino acids. It is a member of the chromogranin family that comprises several proteins. The CgA gene is a single-copy gene localized in the locus 14q32. Chromogranin A is produced by endocrine and neuroendocrine cells. The largest amount of CgA occurs in chromaffin granules of adrenal medulla and in the dense-core vesicles of sympathetic nerves. Its biological functions have not been completely elucidated, but it is known that it acts as a precursor of many biologically active peptides generated by cleavage at specific sites. It is the major soluble protein co-stored and co-released along with resident catecholamines and polypeptide hormones or cell-specific neurotransmitters. Because of its widespread distribution in neuroendocrine tissue, it can be used both as immunohistochemical marker and serum marker of neuroendocrine tuReceived April 6, 2011. Accepted May 20, 2011. The article is supported by the research project MSMT 0021620808 from the Ministry of Education, Youth and Sports of the Czech Republic. Corresponding author: Oldřich Louthan, 4 Department of Medicine – Department of Gastroenterology and Hepatology, First Faculty of Medicine and General University Hospital, Charles University in Prague, U nemocnice 2, 120 00 Prague 2, Czech Republic. e-mail: [email protected] Abbreviations: ACTH – adrenocorticotropic hormone, BAM1745 – 1745-dalton pyroglutamyl peptide, CgA – chromogranin A, CgB – chromogranin B, CgC – chromogranin C (= secretogranin II), DNES – diffuse neuroendocrine system, ECL – enterochromaffin-like, ELISA – enzyme-linked immunosorbent assay, FSH – follicle-stimulating hormone, GAWK – chromogranin B 420–493, GH – growth hormone, IRMA – immunoradiometric assay, LH – luteinizing hormone, MEN 1 – multiple endocrine neoplasia, type 1, NET – neuroendocrine tumour, RIA – radioimmunoassay, SgI – secretogranin I, SgII – secretogranin II, SgIII – secretogranin III, SgIV – secretogranin IV, NESP55 – neuroendocrine secretory protein 55, TSH – thyroid-stimulating hormone. mours. CgA has been used as a rather reliable tumour marker because its level is significantly increased in neuroendocrine tumours and changes of its level reflect the tumour response to therapy or tu-