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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 (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 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 Citing Articles via Google Scholar Google Scholar Articles by Pucci, F. Articles by De Palma, M. Search for Related Content PubMed PubMed Citation Articles by Pucci, F. Articles by De Palma, M. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 21, 2009 Accepted April 9, 2009 A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes (TEMs), blood "resident" monocytes and embryonic macrophages suggests common functions and developmental relationships Ferdinando Pucci, Mary Anna Venneri, Daniela Biziato, Alessandro Nonis, Davide Moi, Antonio Sica, Clelia Di Serio, Luigi Naldini*, and Michele De Palma Angiogenesis and Tumor Targeting Research Unit, San Raffaele Institute, Milan, Italy San Raffaele-Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Institute, Milan, Italy University Centre of Statistics for Biomedical Sciences, Vita Salute San Raffaele University, Milan, Italy Fondazione Humanitas per la Ricerca, Rozzano, Milan, Italy Vita-Salute San Raffaele University Medical School, Milan, Italy * Corresponding author; email: naldini.luigi{at}hsr.it. 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), Gr1+Cd11b+ neutrophils/myeloid-derived suppressor cells, circulating "inflammatory" and "resident" monocytes and tumor-derived endothelial cells (ECs) by qPCR-based gene arrays. TEMs sharply differed from tumor 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 relevant 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 two 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 play important roles 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 physiological proangiogenic and tissue-remodeling programs, which can be co-opted 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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