[{"isi":1,"has_accepted_license":"1","day":"18","dc":{"type":["info:eu-repo/semantics/article","doc-type:article","text","http://purl.org/coar/resource_type/c_6501"],"publisher":["Frontiers"],"date":["2021"],"identifier":["https://research-explorer.ista.ac.at/record/10536","https://research-explorer.ista.ac.at/download/10536/10539"],"description":["TGFβ overexpression is commonly detected in cancer patients and correlates with poor prognosis and metastasis. Cancer progression is often associated with an enhanced recruitment of myeloid-derived cells to the tumor microenvironment. Here we show that functional TGFβ-signaling in myeloid cells is required for metastasis to the lungs and the liver. Myeloid-specific deletion of Tgfbr2 resulted in reduced spontaneous lung metastasis, which was associated with a reduction of proinflammatory cytokines in the metastatic microenvironment. Notably, CD8+ T cell depletion in myeloid-specific Tgfbr2-deficient mice rescued lung metastasis. Myeloid-specific Tgfbr2-deficiency resulted in reduced liver metastasis with an almost complete absence of myeloid cells within metastatic foci. On contrary, an accumulation of Tgfβ-responsive myeloid cells was associated with an increased recruitment of monocytes and granulocytes and higher proinflammatory cytokine levels in control mice. Monocytic cells isolated from metastatic livers of Tgfbr2-deficient mice showed increased polarization towards the M1 phenotype, Tnfα and Il-1β expression, reduced levels of M2 markers and reduced production of chemokines responsible for myeloid-cell recruitment. No significant differences in Tgfβ levels were observed at metastatic sites of any model. These data demonstrate that Tgfβ signaling in monocytic myeloid cells suppresses CD8+ T cell activity during lung metastasis, while these cells actively contribute to tumor growth during liver metastasis. Thus, myeloid cells modulate metastasis through different mechanisms in a tissue-specific manner."],"relation":["info:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2021.765151","info:eu-repo/semantics/altIdentifier/issn/2234-943X","info:eu-repo/semantics/altIdentifier/wos/000726603400001","info:eu-repo/semantics/altIdentifier/pmid/34868988"],"source":["Stefanescu C, Van Gogh M, Roblek M, Heikenwalder M, Borsig L. TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. Frontiers in Oncology. 2021;11. doi:10.3389/fonc.2021.765151"],"title":["TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms"],"subject":["ddc:610"],"language":["eng"],"rights":["info:eu-repo/semantics/openAccess"],"creator":["Stefanescu, Cristina","Van Gogh, Merel","Roblek, Marko","Heikenwalder, Mathias","Borsig, Lubor"]},"publication":"Frontiers in Oncology","uri_base":"https://research-explorer.ista.ac.at","date_published":"2021-11-18T00:00:00Z","date_created":"2021-12-12T23:01:27Z","acknowledgement":"The authors acknowledge the assistance of the Laboratory Animal Services Center (LASC) – UZH, Center for Microscopy and Image Analysis, and the Flow Cytometry Center of the University of Zurich.","quality_controlled":"1","oa":1,"citation":{"apa":"Stefanescu, C., Van Gogh, M., Roblek, M., Heikenwalder, M., & Borsig, L. (2021). TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. Frontiers in Oncology. Frontiers. https://doi.org/10.3389/fonc.2021.765151","short":"C. Stefanescu, M. Van Gogh, M. Roblek, M. Heikenwalder, L. Borsig, Frontiers in Oncology 11 (2021).","ieee":"C. Stefanescu, M. Van Gogh, M. Roblek, M. Heikenwalder, and L. Borsig, “TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms,” Frontiers in Oncology, vol. 11. Frontiers, 2021.","mla":"Stefanescu, Cristina, et al. “TGFβ Signaling in Myeloid Cells Promotes Lung and Liver Metastasis through Different Mechanisms.” Frontiers in Oncology, vol. 11, 765151, Frontiers, 2021, doi:10.3389/fonc.2021.765151.","ista":"Stefanescu C, Van Gogh M, Roblek M, Heikenwalder M, Borsig L. 2021. TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. Frontiers in Oncology. 11, 765151.","chicago":"Stefanescu, Cristina, Merel Van Gogh, Marko Roblek, Mathias Heikenwalder, and Lubor Borsig. “TGFβ Signaling in Myeloid Cells Promotes Lung and Liver Metastasis through Different Mechanisms.” Frontiers in Oncology. Frontiers, 2021. https://doi.org/10.3389/fonc.2021.765151."},"dini_type":"doc-type:article","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"last_name":"Stefanescu","first_name":"Cristina"},{"first_name":"Merel","last_name":"Van Gogh"},{"orcid":"0000-0001-9588-1389","last_name":"Roblek","first_name":"Marko","id":"3047D808-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Heikenwalder","first_name":"Mathias"},{"last_name":"Borsig","first_name":"Lubor"}],"article_processing_charge":"No","external_id":{"pmid":[],"isi":[]},"article_number":"765151","publication_identifier":{"eissn":[]},"publication_status":"published","file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"10539","checksum":"56cbac80e6891ce750511a30161b7792","success":1,"creator":"alisjak","date_updated":"2021-12-13T13:32:37Z","file_size":9245199,"date_created":"2021-12-13T13:32:37Z","file_name":"2021_Frontiers_Stefanescu.pdf"}],"language":[{}],"volume":11,"abstract":[{"lang":"eng"}],"pmid":1,"oa_version":"Published Version","scopus_import":"1","month":"11","intvolume":" 11","date_updated":"2023-08-17T06:20:32Z","creator":{"login":"alisjak","id":"ea97e931-d5af-11eb-85d4-e6957dddbf17"},"ddc":[],"department":[{"_id":"DaSi","tree":[{"_id":"ResearchGroups"},{"_id":"IST"}]}],"file_date_updated":"2021-12-13T13:32:37Z","_id":"10536","article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public"}]