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, Luigi Naldini

Research output: Contribution to journalArticle

311 Citations (Scopus)

Abstract

Tumor-infiltrating myeloid cells, including tumor-associated macrophages (TAMs), have been implicated in tumor progression. We recently described a lineage of mouse monocytes characterized by expression of the Tie2 angiopoietin receptor and required for the vascularization and growth of several tumor 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% to 7% of blood mononuclear cells in healthy 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 tumors, where they represented the main monocyte population distinct from TAMs. Conversely, TEMs were hardly detected in nonneoplastic tissues. In vitro, TEMs migrated toward angiopoietin-2, a TIE2 ligand released by activated endothelial cells and angiogenic vessels, suggesting a homing mechanism for TEMs to tumors. Purified human TEMs, but not TEM-depleted monocytes, markedly promoted angiogenesis in xenotransplanted human tumors, 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.

Original languageEnglish (US)
Pages (from-to)5276-5285
Number of pages10
JournalBlood
Volume109
Issue number12
DOIs
StatePublished - Jun 15 2007
Externally publishedYes

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Tumors
Monocytes
Blood
Neoplasms
Macrophages
Endothelial cells
Angiopoietins
Angiopoietin-2
TIE-2 Receptor
Tissue
Ligands
Myeloid Cells
Population
Blood Cells
Endothelial Cells
Tissue Donors

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Venneri, M. A., De Palma, M., Ponzoni, M., Pucci, F., Scielzo, C., Zonari, E., ... Naldini, L. (2007). Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. Blood, 109(12), 5276-5285. https://doi.org/10.1182/blood-2006-10-053504

Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. / Venneri, Mary Anna; De Palma, Michele; Ponzoni, Maurilio; Pucci, Ferdinando; Scielzo, Cristina; Zonari, Erika; Mazzieri, Roberta; Doglioni, Claudio; Naldini, Luigi.

In: Blood, Vol. 109, No. 12, 15.06.2007, p. 5276-5285.

Research output: Contribution to journalArticle

Venneri, MA, De Palma, M, Ponzoni, M, Pucci, F, Scielzo, C, Zonari, E, Mazzieri, R, Doglioni, C & Naldini, L 2007, 'Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer', Blood, vol. 109, no. 12, pp. 5276-5285. https://doi.org/10.1182/blood-2006-10-053504
Venneri, Mary Anna ; De Palma, Michele ; Ponzoni, Maurilio ; Pucci, Ferdinando ; Scielzo, Cristina ; Zonari, Erika ; Mazzieri, Roberta ; Doglioni, Claudio ; Naldini, Luigi. / Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. In: Blood. 2007 ; Vol. 109, No. 12. pp. 5276-5285.
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