Myeloid Cells Contribute to Tumor Lymphangiogenesis 英文参考文献.docVIP

MyeloidCellsContributetoTumorLymphangiogenesis AdrianZumsteg1.,VanessaBaeriswyl1.,NatsukoImaizumi2,RetoSchwendener3,CurzioRu¨egg2, GerhardChristofori1* 1Institute of Biochemistry and Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland, 2Centre Pluridisciplinaire d’Oncologie, Lausanne Cancer Center,Epalinges,Switzerland,3InstituteforMolecularCancerResearch,UniversityofZu¨rich,Zu¨rich,Switzerland Abstract Theformationofnewbloodvessels(angiogenesis)andlymphaticvessels(lymphangiogenesis)promotestumoroutgrowth and metastasis. Previously, it has been demonstrated that bone marrow-derived cells (BMDC) can contribute to tumor angiogenesis. However, the role of BMDC in lymphangiogenesis has largely remained elusive. Here, we demonstrate by bone marrow transplantation/reconstitution and genetic lineage-tracing experiments that BMDC integrate into tumor- associated lymphatic vessels in the Rip1Tag2 mouse model of insulinoma and in the TRAMP-C1 prostate cancer transplantation model, and that the integrated BMDC originate from the myelomonocytic lineage. Conversely, pharmacological depletion of tumor-associated macrophages reduces lymphangiogenesis. No cell fusion events are detectedbygenetictracingexperiments.Rather,thephenotypicalconversionofmyeloidcellsintolymphaticendothelial cellsandtheirintegrationintolymphaticstructuresisrecapitulatedintwoinvitrotubeformationassaysandisdependent on fibroblast growth factor-mediated signaling. Together, the results reveal that myeloid cells can contribute to tumor- associated lymphatic vessels, thus extending the findings on the previously reported role of hematopoietic cells in lymphaticvesselformation. Citation:ZumstegA,BaeriswylV,ImaizumiN,SchwendenerR,Ru¨eggC,etal.(2009)MyeloidCellsContributetoTumorLymphangiogenesis.PLoSONE4(9): e7067.doi:10.1371/journal.pone.0007067 Editor:SuiHuang,UniversityofCalgary,Canada ReceivedMay5,2009;AcceptedAugust25,2009;PublishedSeptember17,2009 Copyright: ? 2009 Zumsteg et al.