Summary

The trefoil factor family (TFF) is a relatively new family of peptides which bear the three-loop trefoil domain. They are mainly synthesised and secreted by mucin secreting epithelial cells lining the gastrointestinal tract and have a close association with mucins. They are highly conserved during evolution and are heat, acid and enzyme resistant. Their abundant expression in distinct patterns in the normal physiological state and ectopic expression in various ulcerative conditions suggests an important role in mucosal defence and repair. Expression of TFF peptides in neoplasia has stimulated interest in deducing the biological role of these peptides in tumour progression. The underlying molecular mechanism of TFF peptide action is still unknown, but their physical properties, and the biological activities of these peptides as motogens may prove to be useful as therapeutic agents in ulcerative conditions, including inflammatory bowel disease where present treatment is far from ideal.

In humans, three trefoil peptides or trefoil factors (TFF) are known. The first trefoil peptide discovered was pS2/TFF1 or breast cancer oestrogen inducible gene— discovered during a search for oestrogen induced mRNAs from the mammary carcinoma cell line MCF7 in 1982.1 In the same year, TFF2 (formerly spasmolytic polypeptide, SP) was purified and extracted from porcine pancreas during the preparation of porcine insulin.2-4 Several years later, it was noticed that these peptides share a common novel sequence motif,5 ,6 later named the trefoil domain7 or P-domain (fig 1).8 The third mammalian protein in the family, ITF/TFF3 (previously called intestinal trefoil factor, ITF or hP1.B) was later discovered as a rat cDNA sequence in 19919 and the human cDNA sequence was reported in 1993.10-12 These peptides are resistant to thermal and enzymatic digestion, largely because the TFF domain shows a structure tightly held together by three …