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Trefoil
Factor-2, Human Spasmolytic Polypeptide, Promotes Branching Morphogenesis
in MCF-7 Cells |
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El Nasir
Lalani, Ross Williams, Yogi Jayaram, Chris Gilbert, Khurram S. Chaudhary,
Lai-San Siu, Anna Koumarianou, Ray Playford, and Gordon W.H. Stamp |
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DDepartment
of Histopathology (ENL, RW, KSC, L-SS, AK, GWHS); Imperial College of Science,
Technology and Medicine, Hammersmith Hospital, London; Imperial Cancer Research
Fund (YJ, CG), London; and Gastroenterology Research Unit (RP), Leicester
General Hospital, Leicester, United Kingdom. |
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Members of the trefoil factor
(TFF) family are highly expressed in endodermal ulcerative wound healing
and selectively in neoplastic proliferation of various glandular epithelia.
There is some evidence that TFF1 and TFF3 affect cell motility, are indirectly
involved in growth suppression, and are associated with mucin expression.
TFF2 is co-expressed with TFF1 in gastric surface epithelial cells, but
its potential role in vivo is unclear. We analyzed potential effects on
cell proliferation and morphogenesis of TFF2 on a panel of epithelial and
mesenchymal cell lines. TFF2 had no measurable effect on the proliferation
of any of the cell lines tested. In type 1 collagen lattices, TFF2 at a
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 using TFF1. TFF2-treated MCF-7 colonies
showed a 30% reduction in the number of apoptotic bodies, corroborated by
trypan blue exclusion and DNA fragmentation ELISA, indicating TFF2 promotes
cell survival via inhibition of apoptosis and can act as a morphogen in
the presence of TFF1. These properties may complement the actions of TFF1
as a motogen and may explain differential expression in endodermal wound
healing. (Lab Invest, 79:537-546) |
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