Peptidomic and bioinformatic studies on neuroendocrine tumour cells

Neuroendocrine tumours are rich sources of bioactive peptides and potentially-active fragments of proteins. As the cells that constitute such tumours have active regulated secretory pathways, they constantly deliver cocktails of these peptides into the circulation (tumours) or into the culture medium (cells). Many of these peptides may contribute to distinctive clinical tumour syndromes or may be involved in the growth and metastasis of the tumours themselves. This project, the first of its kind, was directed at the molecular inventory of the secretory peptidome of these tumours by application of high-throughput LC/MS/MS techniques. Individual peptides have been structurally-characterized and their parent proteins identified using bioinformatic techniques. They were then sorted into protein types, such as catalytic, structural, regulatory, etc., and comparisons made between individual tumour types to assess numbers of both common and unique components. Selected peptides were chemically-synthesized and subjected to appropriate bioassays. This project provides a body of basic information that may be of use to basic scientists and clinicians.