Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors.
Bone marrow-derived cells contribute to tumor angiogenesis. Here, we demonstrate that monocytes expressing the Tie2 receptor (Tie2-expressing monocytes [TEMs]) (1) are a distinct hematopoietic lineage of proangiogenic cells, (2) are selectively recruited to spontaneous and orthotopic tumors, (3) promote angiogenesis in a paracrine manner, and (4) account for most of the proangiogenic activity of myeloid cells in tumors. Remarkably, TEM knockout completely prevented human glioma neovascularization in the mouse brain and induced substantial tumor regression. Besides TEMs and endothelial cells (ECs), Tie2 expression distinguished a rare population of tumor stroma-derived mesenchymal progenitors representing a primary source of tumor pericytes. Therefore, Tie2 expression characterizes three distinct cell types required for tumor neovascularization: ECs, proangiogenic cells of hematopoietic origin, and pericyte precursors of mesenchymal origin.
De Palma
Michele
M
Angiogenesis and Tumor Targeting Research Unit, San Raffaele Institute, Milano, Italy.
Venneri
Mary Anna
MA
Galli
Rossella
R
Sergi Sergi
Lucia
L
Politi
Letterio S
LS
Sampaolesi
Maurilio
M
Naldini
Luigi
L
D000818:Animals; D017930:Genes, Reporter; D005822:Genetic Vectors; D005909:Glioblastoma / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D008822:Mice, Transgenic; D009000:Monocytes / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D010190:Pancreatic Neoplasms / Q000473:pathology; D020286:Pericytes / Q000473:pathology*; D042787:Receptor, TIE-2 / Q000502:physiology*; D013234:Stem Cells / Q000473:pathology; D014183:Transplantation, Heterologous
D049452:Green Fluorescent Proteins; D042787:Receptor, TIE-2