Trefoil peptides

Abstract

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 pairs of disulphide bonds, which is encoded by shuffled modules highly conserved during evolution from amphibians to mammals (fig 1). TFF1 and TFF3 contain one trefoil domain, TFF2 has two and in the amphibianXenopus, there are molecules containing multiple trefoil domains.13-16 All three human trefoil genes are clustered on chromosome 21q22.3.17-21 The present nomenclature is based on the work of a group at a Conférence Philippe Laudat in which pS2 was named TFF1, spasmolytic polypeptide TFF2 and intestinal trefoil factor TFF3. It was recommended that different species be indicated by a lower case letter prefixed to the peptide name—for example, hTFF1 for human pS2, rTFF3 for rat ITF, etc.22 This article will mainly focus on recent proposals for the role of these peptides in epithelial inflammation, repair, and neoplasia in the gastrointestinal tract.