[{"_id":"10536","title":"TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"DaSi"}],"fulldoi":"https://doi.org/10.3389/fonc.2021.765151","publication_identifier":{"eissn":["2234-943X"]},"day":"18","file":[{"content_type":"application/pdf","file_id":"10539","date_created":"2021-12-13T13:32:37Z","file_name":"2021_Frontiers_Stefanescu.pdf","file_size":9245199,"creator":"alisjak","checksum":"56cbac80e6891ce750511a30161b7792","access_level":"open_access","success":1,"date_updated":"2021-12-13T13:32:37Z","relation":"main_file"}],"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"doi":"10.3389/fonc.2021.765151","oa":1,"volume":11,"has_accepted_license":"1","external_id":{"isi":["000726603400001"],"pmid":["34868988"]},"article_type":"original","article_processing_charge":"No","type":"journal_article","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"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."}],"quality_controlled":"1","status":"public","scopus_import":"1","date_updated":"2023-08-17T06:20:32Z","author":[{"full_name":"Stefanescu, Cristina","last_name":"Stefanescu","first_name":"Cristina"},{"last_name":"Van Gogh","first_name":"Merel","full_name":"Van Gogh, Merel"},{"orcid":"0000-0001-9588-1389","last_name":"Roblek","first_name":"Marko","full_name":"Roblek, Marko","id":"3047D808-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Heikenwalder","first_name":"Mathias","full_name":"Heikenwalder, Mathias"},{"full_name":"Borsig, Lubor","first_name":"Lubor","last_name":"Borsig"}],"intvolume":"        11","article_number":"765151","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.","isi":1,"file_date_updated":"2021-12-13T13:32:37Z","publication_status":"published","date_created":"2021-12-12T23:01:27Z","year":"2021","publication":"Frontiers in Oncology","oa_version":"Published Version","citation":{"mla":"Stefanescu, Cristina, et al. “TGFβ Signaling in Myeloid Cells Promotes Lung and Liver Metastasis through Different Mechanisms.” <i>Frontiers in Oncology</i>, vol. 11, 765151, Frontiers, 2021, doi:<a href=\"https://doi.org/10.3389/fonc.2021.765151\">10.3389/fonc.2021.765151</a>.","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.” <i>Frontiers in Oncology</i>. Frontiers, 2021. <a href=\"https://doi.org/10.3389/fonc.2021.765151\">https://doi.org/10.3389/fonc.2021.765151</a>.","apa":"Stefanescu, C., Van Gogh, M., Roblek, M., Heikenwalder, M., &#38; Borsig, L. (2021). TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. <i>Frontiers in Oncology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fonc.2021.765151\">https://doi.org/10.3389/fonc.2021.765151</a>","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,” <i>Frontiers in Oncology</i>, vol. 11. Frontiers, 2021.","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.","ama":"Stefanescu C, Van Gogh M, Roblek M, Heikenwalder M, Borsig L. TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. <i>Frontiers in Oncology</i>. 2021;11. doi:<a href=\"https://doi.org/10.3389/fonc.2021.765151\">10.3389/fonc.2021.765151</a>"},"publisher":"Frontiers","month":"11","ddc":["610"],"date_published":"2021-11-18T00:00:00Z","pmid":1}]