Trefoil factor-2, human spasmolytic polypeptide, promotes branching morphogenesis in MCF-7 cells

Members of the trefoil factor (TFF) family are highly expressed in endoderm al ulcerative wound healing and selectively in neoplastic proliferation of various glandular epithelia. There is some evidence that TFF1 and TFF3 affe ct cell motility, are indirectly involved in growth suppression, and are as sociated with mucin expression. TFF2 is co-expressed with TFF1 in gastric s urface epithelial cells, but its potential role in vivo is unclear. We anal yzed potential effects on cell proliferation and morphogenesis of TFF2 on a panel of epithelial and mesenchymal cell lines. TFF2 had no measurable eff ect on the proliferation of any of the cell lines tested. In type 1 collage n lattices, TFF2 ata low concentration (25-100 nM) induced the formation of highly complex branched structures in the breast carcinoma cell line MCF-7 over a period of 14 to 42 days. No significant effect was shown with other cell lines. This morphogenic effect was abolished by monoclonal antibodies specific for either TFF2 or TFF1. TFF2 did not affect cell motility in MCF -7 cells as measured by videomicroscopy, in contrast to previous studies us ing TFF1. TFF2-treated MCF-7 colonies showed a 30% reduction in the number of apoptotic bodies, corroborated by trypan blue exclusion and DNA fragment ation ELISA, indicating TFF2 promotes cell survival via inhibition of apopt osis and can act as a morphogen in the presence of TFFI. These properties m ay complement the actions of TFFI as a motogen and may explain differential expression in endodermal wound healing.