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Blood, 23 July 2009, Vol. 114, No. 4, pp. 901-914. Prepublished online as a Blood First Edition Paper on April 21, 2009; DOI 10.1182/blood-2009-01-200931. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2009-01-200931v1 114/4/901    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Pucci, F. Articles by De Palma, M. PubMed PubMed Citation Articles by Pucci, F. Articles by De Palma, M. Related Collections Phagocytes, Granulocytes, and Myelopoiesis Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships Ferdinando Pucci13,*, Mary Anna Venneri1,2,*, Daniela Biziato1,2, Alessandro Nonis4, Davide Moi1,2, Antonio Sica5, Clelia Di Serio4, Luigi Naldini13,, and Michele De Palma1,2, 1 Angiogenesis and Tumor Targeting Research Unit, San Raffaele Institute, Milan; 2 San Raffaele-Telethon Institute for Gene Therapy, San Raffaele Institute, Milan; 3 Vita-Salute San Raffaele University Medical School, Milan; 4 University Centre of Statistics for Biomedical Sciences, Vita Salute San Raffaele University, Milan; and 5 Fondazione Humanitas per la Ricerca, Rozzano, Milan; and DiSCAFF and University of Piemonte Orientale A. Avogadro, Novara, Italy We previously showed that Tie2-expressing monocytes (TEMs) have nonredundant proangiogenic activity in tumors. Here, we compared the gene expression profile of tumor-infiltrating TEMs with that of tumor-associated macrophages (TAMs), spleen-derived Gr1+Cd11b+ neutrophils/myeloid-derived suppressor cells, circulating "inflammatory" and "resident" monocytes, and tumor-derived endothelial cells (ECs) by quantitative polymerase chain reaction–based gene arrays. TEMs sharply differed from ECs and Gr1+Cd11b+ cells but were highly related to TAMs. Nevertheless, several genes were differentially expressed between TEMs and TAMs, highlighting a TEM signature consistent with enhanced proangiogenic/tissue-remodeling activity and lower proinflammatory activity. We validated these findings in models of oncogenesis and transgenic mice expressing a microRNA-regulated Tie2-GFP reporter. Remarkably, resident monocytes and TEMs on one hand, and inflammatory monocytes and TAMs on the other hand, expressed coordinated gene expression profiles, suggesting that the 2 blood monocyte subsets are committed to distinct extravascular fates in the tumor microenvironment. We further showed that a prominent proportion of embryonic/fetal macrophages, which participate in tissue morphogenesis, expressed distinguishing TEM genes. It is tempting to speculate that Tie2+ embryonic/fetal macrophages, resident blood monocytes, and tumor-infiltrating TEMs represent distinct developmental stages of a TEM lineage committed to execute physiologic proangiogenic and tissue-remodeling programs, which can be coopted by tumors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Judging a proangiogenic cell by its cover Mervin C. Yoder Blood 2009 114: 756-757. [Full Text] [PDF] This article has been cited by other articles: M. C. Yoder Judging a proangiogenic cell by its cover Blood, July 23, 2009; 114(4): 756 - 757. [Full Text] [PDF]

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