Theranostics 2021; 11(16):7671-7684. doi:10.7150/thno.61881 This issue Cite

Research Paper

Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors

David Cabrerizo-Granados1,2*, Raúl Peña1*, Laura Palacios1, Laura Carrillo-Bosch1, Josep Lloreta-Trull2,3, Laura Comerma3, Mar Iglesias3, Antonio García de Herreros1,2✉

1. Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Unidad Asociada al CSIC, Barcelona, Spain.
2. Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
3. Servei d'Anatomia Patològica, Hospital del Mar, Barcelona, Spain.
* These authors contributed equally to this work.

Citation:
Cabrerizo-Granados D, Peña R, Palacios L, Carrillo-Bosch L, Lloreta-Trull J, Comerma L, Iglesias M, de Herreros AG. Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors. Theranostics 2021; 11(16):7671-7684. doi:10.7150/thno.61881. https://www.thno.org/v11p7671.htm
Other styles

File import instruction

Abstract

Graphic abstract

Snail1 is a transcriptional factor required for epithelial to mesenchymal transition and activation of cancer-associated fibroblasts (CAF). Apart from that, tumor endothelial cells also express Snail1. Here, we have unraveled the role of Snail1 in this tissue in a tumorigenic context.

Methods: We generated transgenic mice with an endothelial-specific and inducible Snail1 depletion. This murine line was crossed with MMTV-PyMT mice that develop mammary gland tumors and the consequence of Snail1 depletion in the endothelium were investigated. We also interfere Snail1 expression in cultured endothelial cells.

Results: Specific Snail1 depletion in the endothelium of adult mice does not promote an overt phenotype; however, it delays the formation of mammary gland tumors in MMTV-PyMT mice. These effects are associated to the inability of Snail1-deficient endothelial cells to undergo angiogenesis and to enhance CAF activation in a paracrine manner. Moreover, tumors generated in mice with endothelium-specific Snail1 depletion are less advanced and show a papillary phenotype. Similar changes on onset and tumor morphology are observed by pretreatment of MMTV-PyMT mice with the angiogenic inhibitor Bevacizumab. Human breast papillary carcinomas exhibit a lower angiogenesis and present lower staining of Snail1, both in endothelial and stromal cells, compared with other breast neoplasms. Furthermore, human breast tumors datasets show a strong correlation between Snail1 expression and high angiogenesis.

Conclusion: These findings show a novel role for Snail1 in endothelial cell activation and demonstrate that these cells impact not only on angiogenesis, but also on tumor onset and phenotype.


Citation styles

APA
Cabrerizo-Granados, D., Peña, R., Palacios, L., Carrillo-Bosch, L., Lloreta-Trull, J., Comerma, L., Iglesias, M., de Herreros, A.G. (2021). Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors. Theranostics, 11(16), 7671-7684. https://doi.org/10.7150/thno.61881.

ACS
Cabrerizo-Granados, D.; Peña, R.; Palacios, L.; Carrillo-Bosch, L.; Lloreta-Trull, J.; Comerma, L.; Iglesias, M.; de Herreros, A.G. Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors. Theranostics 2021, 11 (16), 7671-7684. DOI: 10.7150/thno.61881.

NLM
Cabrerizo-Granados D, Peña R, Palacios L, Carrillo-Bosch L, Lloreta-Trull J, Comerma L, Iglesias M, de Herreros AG. Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors. Theranostics 2021; 11(16):7671-7684. doi:10.7150/thno.61881. https://www.thno.org/v11p7671.htm

CSE
Cabrerizo-Granados D, Peña R, Palacios L, Carrillo-Bosch L, Lloreta-Trull J, Comerma L, Iglesias M, de Herreros AG. 2021. Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors. Theranostics. 11(16):7671-7684.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image