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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5276-5285. Prepublished online as a Blood First Edition Paper on February 27, 2007; DOI 10.1182/blood-2006-10-053504. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2006-10-053504v1 109/12/5276    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 Venneri, M. A. Articles by Naldini, L. Search for Related Content PubMed PubMed Citation Articles by Venneri, M. A. Articles by Naldini, L. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 20, 2006 Accepted February 19, 2007 Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer Mary Anna Venneri, Michele De Palma, Maurilio Ponzoni, Ferdinando Pucci, Cristina Scielzo, Erika Zonari, Roberta Mazzieri, Claudio Doglioni, and Luigi Naldini* Angiogenesis & Tumour Targeting Research Unit, San Raffaele Scientific Institute, Milan, Italy San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy Dept of Pathology, San Raffaele Scientific Institute, Milan, Italy Dept of Oncology, San Raffaele Scientific Institute, Milan, Italy Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy * Corresponding author; email: naldini.luigi{at}hsr.it. Tumour-infiltrating myeloid cells, including tumour-associated macrophages (TAMs), have been implicated in tumour progression. We recently described a lineage of mouse monocytes characterised by expression of the Tie2 angiopoietin receptor and required for the vascularization and growth of several tumour models. Here, we report that TIE2 expression in human blood identifies a subset of monocytes distinct from classical inflammatory monocytes and comprised within the less abundant "resident" population. These TIE2-expressing monocytes (TEMs) accounted for 2-7% of blood mononuclear cells in normal donors and were distinct from rare circulating endothelial cells and progenitors. In human cancer patients, TEMs were observed in the blood and, intriguingly, within the tumours, where they represented the main monocyte population distinct from TAMs. Conversely, TEMs were hardly detected in non-neoplastic tissues. In vitro, TEMs migrated towards Angiopoietin-2, a TIE2 ligand released by activated endothelial cells and angiogenic vessels, suggesting a homing mechanism for TEMs to tumours. Purified human TEMs, but not TEM-depleted monocytes, markedly promoted angiogenesis in xenotransplanted human tumours, suggesting a potentially critical role of TEMs in human cancer progression. Human TEMs may provide a novel, biologically relevant marker of angiogenesis and represent a previously unrecognized target of cancer therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Monocytes TIE(2)d up in murky business George Coukos Blood 2007 109: 5076. [Full Text] [PDF] This article has been cited by other articles: G. Solinas, G. Germano, A. Mantovani, and P. Allavena Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation J. Leukoc. Biol., November 1, 2009; 86(5): 1065 - 1073. [Abstract] [Full Text] [PDF] C. Folkins, Y. Shaked, S. Man, T. Tang, C. R. Lee, Z. Zhu, R. M. Hoffman, and R. S. Kerbel Glioma Tumor Stem-Like Cells Promote Tumor Angiogenesis and Vasculogenesis via Vascular Endothelial Growth Factor and Stromal-Derived Factor 1 Cancer Res., September 15, 2009; 69(18): 7243 - 7251. [Abstract] [Full Text] [PDF] M. van Meurs, N. F. Kurniati, F. M. Wulfert, S. A. Asgeirsdottir, I. A. de Graaf, S. C. Satchell, P. W. Mathieson, R. M. Jongman, P. Kumpers, J. G. Zijlstra, et al. Shock-induced stress induces loss of microvascular endothelial Tie2 in the kidney which is not associated with reduced glomerular barrier function Am J Physiol Renal Physiol, August 1, 2009; 297(2): F272 - F281. [Abstract] [Full Text] [PDF] F. Pucci, M. A. Venneri, D. Biziato, A. Nonis, D. Moi, A. Sica, C. Di Serio, L. Naldini, and M. De Palma A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships Blood, July 23, 2009; 114(4): 901 - 914. [Abstract] [Full Text] [PDF] N. Figueroa-Vega, M. Alfonso-Perez, C. Cuesta-Mateos, F. Sanchez-Madrid, R. Moreno-Otero, R. Gonzalez-Amaro, and M. Marazuela Tie-2 Is Overexpressed by Monocytes in Autoimmune Thyroid Disorders and Participates in Their Recruitment to the Thyroid Gland J. Clin. Endocrinol. Metab., July 1, 2009; 94(7): 2626 - 2633. [Abstract] [Full Text] [PDF] A. J.G. Horrevoets Angiogenic Monocytes: Another Colorful Blow to Endothelial Progenitors Am. J. Pathol., May 1, 2009; 174(5): 1594 - 1596. [Abstract] [Full Text] [PDF] N. Figueroa-Vega, P. Sanz-Cameno, R. Moreno-Otero, F. Sanchez-Madrid, R. Gonzalez-Amaro, and M. Marazuela Serum Levels of Angiogenic Molecules in Autoimmune Thyroid Diseases and Their Correlation with Laboratory and Clinical Features J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1145 - 1153. [Abstract] [Full Text] [PDF] H. Chen, R. A. Campbell, Y. Chang, M. Li, C. S. Wang, J. Li, E. Sanchez, M. Share, J. Steinberg, A. Berenson, et al. Pleiotrophin produced by multiple myeloma induces transdifferentiation of monocytes into vascular endothelial cells: a novel mechanism of tumor-induced vasculogenesis Blood, February 26, 2009; 113(9): 1992 - 2002. [Abstract] [Full Text] [PDF] B. Li, A. Vincent, J. Cates, D. M. Brantley-Sieders, D. B. Polk, and P. P. Young Low Levels of Tumor Necrosis Factor {alpha} Increase Tumor Growth by Inducing an Endothelial Phenotype of Monocytes Recruited to the Tumor Site Cancer Res., January 1, 2009; 69(1): 338 - 348. [Abstract] [Full Text] [PDF] Errata J. Leukoc. Biol., December 1, 2008; 84(6): 1623a - 1623. [Full Text] [PDF] E. R. Duncan, P. A. 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