myeloid cells contribute to tumor lymphangiogenesis髓细胞为肿瘤lymphangiogenesis作出贡献.pdfVIP

Myeloid Cells Contribute to Tumor Lymphangiogenesis 1. 1. 2 3 ¨ 2 Adrian Zumsteg , Vanessa Baeriswyl , Natsuko Imaizumi , Reto Schwendener , Curzio Ruegg , Gerhard Christofori1* 1 Institute of Biochemistry and Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland, 2 Centre Pluridisciplinaire d’Oncologie, Lausanne Cancer ¨ ¨ Center, Epalinges, Switzerland, 3 Institute for Molecular Cancer Research, University of Zurich, Zurich, Switzerland Abstract The formation of new blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis) promotes tumor outgrowth 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 detected by genetic tracing experiments. Rather, the phenotypical conversion of myeloid cells into lymphatic endothelial cells and their integration into lymphatic structures is recapitulated in