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Trefoil factor-2, human spasmolytic polypeptide, promotes branching morphogenesis in MCF-7 cells
E N Lalani1, R Williams, Y Jayaram
1Department of Histopathology, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London, United Kingdom.
Abstract:
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.
Insights
Trefoil factor 2 (TFF2) promotes cell survival by inhibiting apoptosis and acts as a morphogen in breast cancer cells, complementing TFF1's role in cell motility.
Area of Science:
- Cell biology
- Molecular biology
- Cancer research
Background:
- Trefoil factor (TFF) family members are implicated in epithelial repair and cancer.
- TFF1 and TFF3 influence cell motility and growth suppression.
- The in vivo role of TFF2, often co-expressed with TFF1 in gastric epithelia, remains largely undefined.
Purpose of the Study:
- To investigate the effects of TFF2 on epithelial and mesenchymal cell proliferation and morphogenesis.
- To elucidate the specific mechanisms by which TFF2 influences cell behavior.
Main Methods:
- Cell proliferation assays across various epithelial and mesenchymal cell lines.
- Morphogenesis assays using type I collagen lattices with MCF-7 breast carcinoma cells.
- Analysis of cell motility via videomicroscopy.
- Assessment of apoptosis using trypan blue exclusion and DNA fragmentation ELISA.
Main Results:
- TFF2 did not affect the proliferation of any tested cell lines.
- Low concentrations of TFF2 induced complex branching morphogenesis in MCF-7 cells within collagen lattices over 14-42 days.
- This morphogenic effect was dependent on the presence of TFF1 and abolished by specific antibodies.
- TFF2 inhibited apoptosis in MCF-7 cells by approximately 30%, promoting cell survival.
- TFF2 did not influence cell motility in MCF-7 cells, unlike TFF1.
Conclusions:
- TFF2 functions as a morphogen in specific contexts, notably in breast carcinoma cells (MCF-7), particularly when TFF1 is present.
- TFF2 promotes cell survival by inhibiting apoptosis, suggesting a complementary role to TFF1's motogenic effects.
- These findings offer insights into the differential roles of TFF family members in epithelial repair and neoplastic processes.