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A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery
Published on: February 28, 2020
Expression of Snail protein in tumor-stroma interface
1Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, Barcelona, Spain.
Abstract:
The product of Snail gene is a repressor of E-cadherin transcription and an inductor of the epithelial-to-mesenchymal transition in several epithelial tumor cell lines. In order to examine Snail expression in animal and human tissues, we have raised a monoclonal antibody (MAb) that reacts with the regulatory domain of this protein. Analysis of murine embryos shows that Snail is expressed in extraembryonic tissues and embryonic mesoderm, in mesenchymal cells of lungs and dermis as well as in cartilage. Little reactivity was detected in adult tissues as Snail was not constitutively expressed in most mesenchymal cells. However, Snail expression was observed in activated fibroblasts involved in wound healing in mice skin. Moreover, Snail was detected in pathological conditions causing hyperstimulation of fibroblasts, such as fibromatosis. Analysis of Snail expression in tumors revealed that it was highly expressed in sarcomas and fibrosarcomas. In epithelial tumors, it presented a more limited distribution, restricted to stromal cells placed in the vicinity of the tumor and to tumoral cells in the same areas. These results demonstrate that Snail is present in activated mesenchymal cells, indicate its relevance in the communication between tumor and stroma and suggest that it can promote the conversion of carcinoma cells to stromal cells.
Insights
Snail gene product, a key factor in cell changes, is found in activated mesenchymal cells during wound healing and in fibromatosis. Its expression in tumors suggests a role in tumor-stroma interactions and potential cell conversion.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cancer Biology
Background:
- Snail gene product acts as a repressor of E-cadherin transcription.
- It induces epithelial-to-mesenchymal transition in epithelial tumor cell lines.
Purpose of the Study:
- To examine Snail expression in animal and human tissues.
- To investigate the role of Snail in activated mesenchymal cells and tumors.
Main Methods:
- Developed a monoclonal antibody (MAb) targeting the Snail protein's regulatory domain.
- Analyzed Snail expression in murine embryos, adult tissues, and various tumors (sarcomas, fibrosarcomas, epithelial tumors).
Main Results:
- Snail is expressed in embryonic mesoderm, mesenchymal cells, and cartilage in murine embryos.
- In adult tissues, Snail is found in activated fibroblasts during wound healing and in fibromatosis.
- High Snail expression observed in sarcomas and fibrosarcomas.
- In epithelial tumors, Snail is localized to stromal and adjacent tumoral cells.
Conclusions:
- Snail is present in activated mesenchymal cells.
- Snail plays a role in tumor-stroma communication.
- Snail may promote the conversion of carcinoma cells to stromal cells.
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