Chromogranin a in physiology and oncology

Chromogranin A (CgA) is a hydrophilic acidic one-chain peptide containing 439 amino acids, preceded by NH2-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 tumours. 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 tumour recurrence.