Macrophages form functional vascular mimicry channels in vivo.
Macrophages, key cells of the innate immune system, are known to support angiogenesis but are not believed to directly form vessel walls. Here we show that macrophages structurally form primitive, NON-ENDOTHELIAL "vessels" or vascular mimicry (VM) channels in both tumor and angiogenesis in vivo models. These channels are functionally connected to the systemic vasculature as they are perfused by intravenously injected dye. Since both models share hypoxic micro-environments, we hypothesized that hypoxia may be an important mediator of VM formation. Indeed, conditional genetic depletion of myeloid-specific HIF-1α results in decreased VM network formation, dye perfusion and tumor size. Although the macrophage VM network shares some features with an endothelial vasculature, it is ultrastructurally different. Cancer stem cells have been shown to form vascular mimicry channels. Our data demonstrates that tumor-associated macrophages also form them. The identification of this novel type of vascular mimicry may help in the development of targeted cancer therapeutics.
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
Faith H
FH
Barnett
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
Mauricio
M
Rosenfeld
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
Malcolm
M
Wood
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
William B
WB
Kiosses
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
Yoshihiko
Y
Usui
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
Valentina
V
Marchetti
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
Edith
E
Aguilar
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
Martin
M
Friedlander
D000818:Animals; D001808:Blood Vessels / Q000276:immunology* / Q000473:pathology; D015687:Cell Hypoxia / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000473:pathology