Immune cell recruitment in teratomas is impaired by increased Wnt secretion
| Autor: | Fabian Brunk, Michael Boutros, Eugen Rempel, Dyah L. Dewi, Jennifer Hundshammer, Iris Augustin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Embryonic stem cells Mice SCID Tumor initiation Biology Malignant transformation Mice 03 medical and health sciences Animals Humans Cell Proliferation Medicine(all) Tumor microenvironment Teratoma Wnt signaling pathway Cell Differentiation LRP5 Cell Biology General Medicine Wnt signaling Embryonic stem cell Wnt Proteins Immunosurveillance Immune surveillance 030104 developmental biology Tumor progression Immunology Cancer research Developmental Biology |
| Zdroj: | Stem Cell Research. 17:607-615 |
| ISSN: | 1873-5061 |
| DOI: | 10.1016/j.scr.2016.10.010 |
| Popis: | Wnt signaling plays a central role in tumor initiation and tumor progression. Mutations in Wnt pathway components, such as the tumor suppressor APC, lead to malignant transformation. While previous studies focused on Wnt-related changes in cancer cells, the impact of aberrant Wnt signaling on the tumor microenvironment is only beginning to emerge. In order to investigate the role of increased Wnt secretion on tumor growth and the microenvironment, we generated a novel germ cell tumor model by overexpressing the Wnt secretion factor Evi/Wls in mouse embryonic stem cells. Evi-overexpressing teratoma were characterized by enhanced tumor growth in supporting a tumor-promoting role of Wnt secretion. Interestingly, enhanced Evi expression correlated with impaired immune cell recruitment. Specifically, T- and B-cell infiltration was reduced in Evi-overexpressing teratomas, which was independent of teratoma size and differentiation. Our study suggests that Wnt secretion impairs immunosurveillance. Since immune cell infiltration has been shown to have prognostic value, the levels of secreted Wnt activity might impact the efficiency of cancer immunotherapy. |
| Databáze: | OpenAIRE |
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