Serpin E2 promotes breast cancer metastasis by remodeling the tumor matrix and polarizing tumor associated macrophages

Smirnova, T. and Bonapace, L. and MacDonald, G. and Kondo, S. and Wyckoff, J. and Ebersbach, H. and Fayard, B. and Doelemeyer, A. and Coissieux, M. M. and Heideman, M. R. and Bentires-Alj, M. and Hynes, N. E.. (2016) Serpin E2 promotes breast cancer metastasis by remodeling the tumor matrix and polarizing tumor associated macrophages. Oncotarget, 7 (50). pp. 82289-82304.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/61380/

Downloads: Statistics Overview


The extracellular serine protease inhibitor serpinE2 is overexpressed in breast cancer and has been shown to foster metastatic spread. Here, we investigated the hypothesis that serpinE2 creates tumor-promoting conditions in the tumor microenvironment (TME) by affecting extracellular matrix remodeling. Using two different breast cancer models, we show that blocking serpinE2, either by knock-down (KD) in tumor cells or in response to a serpinE2 binding antibody, decreases metastatic dissemination from primary tumors to the lungs. We demonstrate that in response to serpinE2 KD or antibody treatment there are dramatic changes in the TME. Multiphoton intravital imaging revealed deposition of a dense extracellular collagen I matrix encapsulating serpinE2 KD or antibody-treated tumors. This is accompanied by a reduction in the population of tumor-promoting macrophages, as well as a decrease in chemokine ligand 2, which is known to affect macrophage abundance and polarization. In addition, TIMP-1 secretion is increased, which may directly inhibit matrix metalloproteases critical for collagen degradation in the tumor. In summary, our findings suggest that serpinE2 is required in the extracellular milieu of tumors where it acts in multiple ways to regulate tumor matrix deposition, thereby controlling tumor cell dissemination.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Tumor Heterogeneity Metastasis and Resistance (Bentires-Alj)
UniBasel Contributors:Bentires-Alj, Mohamed
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:22 Jan 2019 18:03
Deposited On:22 Jan 2019 17:55

Repository Staff Only: item control page