Trends in Immunology
OpinionTie2-expressing monocytes: regulation of tumor angiogenesis and therapeutic implications
Section snippets
Role of bone marrow-derived cells in tumor angiogenesis
During physiological angiogenesis, new blood vessels are formed through a well-orchestrated series of events, which include endothelial cell (EC) proliferation, their migration toward angiogenic stimuli, recruitment of perivascular support cells, functional lumen formation, and blood flow 1, 2. During development and organogenesis, the activation of molecular and cellular programs that control angiogenesis is tightly regulated by an assortment of positive and negative mediators (pro- and
Tie2-expressing monocytes and tumor angiogenesis
Although our studies have shown that putative BM-derived EPCs do not incorporate directly into tumor blood vessels, they highlighted the important contribution of hematopoietic-lineage cells in the angiogenic process 13, 23. In particular, we noted that one subset of monocytes plays an essential role in this phenomenon, those expressing the angiopoietin receptor Tie2 (Box 1). The Tie2 tyrosine kinase receptor has been shown previously to be expressed only by endothelial and hematopoietic stem
Possible role of TEMs in other diseases
We investigated the recruitment of TEMs to sites of angiogenesis other than tumors. We analysed the recruitment of gene-marked TEMs in mice that underwent partial hepatectomy 7–10 days earlier, and we found that TEMs were present in the granulation tissue surrounding the regenerating hepatic lobules [13]. Some TEMs were found in proximity to newly formed vessels, similar to tumor TEMs, suggesting that they might also contribute to promoting angiogenesis during liver regeneration. Other reports
Therapeutic opportunities: targeting TEMs or exploiting them as gene-delivery vehicles in anticancer therapy
The future identification of specific molecules expressed by TEMs in tumors could facilitate the design of novel anticancer therapies that selectively target these cells, thereby removing their proangiogenic contribution in such tissues while preserving their potential role in regulating tissue homeostasis and immunity (Box 2). The identification of gene expression by TEMs in tumors and the tumor microenvironmental factors that regulate TEM recruitment and/or function probably highlight such
Acknowledgements
C.M. and C.E.L. would like to thank Yorkshire Cancer Campaign and Breast Cancer Campaign for grant support of their work in this area. L.N. acknowledges the grant support from Associazione Italiana per la Ricerca sul Cancro (AIRC 52–2005), European Union (Tumor-Host Genomics, LSHC-CT-2005–518198), and Telethon (TIGET). M.D.P. was supported by AIRC. None of the authors have a financial interest in this work.
References (48)
- et al.
Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis
Cell
(1996) Human CD34(+)AC133(+)VEGFR-2(+) cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors
Exp. Hematol.
(2007)Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium
Blood
(2004)Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors
Cancer Cell
(2003)- et al.
Role of bone marrow-derived cells in tumor angiogenesis and treatment
Cancer Cell
(2003) - et al.
Role of haematopoietic cells and endothelial progenitors in tumour angiogenesis
Biochim. Biophys. Acta
(2006) Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors
Cancer Cell
(2005)Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues
Blood
(2004)The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis
Trends Immunol.
(2007)Smoldering and polarized inflammation in the initiation and promotion of malignant disease
Cancer Cell
(2005)
Extrinsic regulators of epithelial tumor progression: metalloproteinases
Curr. Opin. Genet. Dev.
The role of tumor stroma in the interaction between tumor and immune system
Curr. Opin. Immunol.
Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer
Blood
Expression of angiopoietin-2 by human endometrial endothelial cells: regulation by hypoxia and inflammation
Biochem. Biophys. Res. Commun.
Macrophage responses to hypoxia: implications for tumor progression and anti-cancer therapies
Am. J. Pathol.
Tumour necrosis factor and cancer
Prog. Growth Factor Res.
Differential activation of vascular genes by hypoxia in primary endothelial cells
Exp. Cell Res.
Angiopoietins: a link between angiogenesis and inflammation
Trends Immunol.
Angiogenesis in life, disease and medicine
Nature
Molecular regulation of vessel maturation
Nat. Med.
Angiogenesis in cancer and other diseases
Nature
Imaging of angiogenesis: from microscope to clinic
Nat. Med.
Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy?
Nat. Rev. Cancer
Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration
Nat. Med.
Cited by (238)
UTMD inhibits pancreatic cancer growth and metastasis by inducing macrophage polarization and vessel normalization
2023, Biomedicine and PharmacotherapyTo kill a cancer: Targeting the immune inhibitory checkpoint molecule, B7-H3
2022, Biochimica et Biophysica Acta - Reviews on Cancer