Elusive Identities and Overlapping Phenotypes of Proangiogenic Myeloid Cells in Tumors

Medical School, University of Sheffield, Sheffield, S10 2RX, UK.
American Journal Of Pathology (Impact Factor: 4.59). 02/2010; 176(4):1564-76. DOI: 10.2353/ajpath.2010.090786
Source: PubMed


It is now established that bone marrow-derived myeloid cells regulate tumor angiogenesis. This was originally inferred from studies of human tumor biopsies in which a positive correlation was seen between the number of tumor-infiltrating myeloid cells, such as macrophages and neutrophils, and tumor microvessel density. However, unequivocal evidence was only provided once mouse models were used to examine the effects on tumor angiogenesis by genetically or pharmacologically targeting myeloid cells. Since then, identifying the exact myeloid cell types involved in this process has proved challenging because of myeloid cell heterogeneity and the expression of overlapping phenotypic markers in tumors. As a result, investigators often simply refer to them now as "bone marrow-derived myeloid cells." Here we review the findings of various attempts to phenotype the myeloid cells involved and discuss the therapeutic implications of correctly identifying-and thus being able to target-this proangiogenic force in tumors.

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Available from: Seth Coffelt, Nov 05, 2014
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    • "Tie2-expressing macrophages (TEMs) represent a TAM subset closely associated with the vasculature (33, 34). These cells appear to have a distinct gene signature (35) in spite of substantial overlaps between TAMs, TEMs, myeloid-derived suppressor cells (MDSCs), monocytes, and embryonic/fetal macrophages (35, 36). TEMs are also recruited at the tumor site after treatment with vascular disrupting agents, interfering with and antagonizing their action (37). "
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    ABSTRACT: It is widely accepted that the tumor microenvironment (TUMIC) plays a major role in cancer and is indispensable for tumor progression. The TUMIC involves many "players" going well beyond the malignant-transformed cells, including stromal, immune, and endothelial cells (ECs). The non-malignant cells can acquire tumor-promoting functions during carcinogenesis. In particular, these cells can "orchestrate" the "symphony" of the angiogenic switch, permitting the creation of new blood vessels that allows rapid expansion and progression toward malignancy. Considerable attention within the context of tumor angiogenesis should focus not only on the ECs, representing a fundamental unit, but also on immune cells and on the inflammatory tumor infiltrate. Immune cells infiltrating tumors typically show a tumor-induced polarization associated with attenuation of anti-tumor functions and generation of pro-tumor activities, among these angiogenesis. Here, we propose a scenario suggesting that the angiogenic switch is an immune switch arising from the pro-angiogenic polarization of immune cells. This view links immunity, inflammation, and angiogenesis to tumor progression. Here, we review the data in the literature and seek to identify the "conductors" of this "orchestra." We also suggest that interrupting the immune → inflammation → angiogenesis → tumor progression process can delay or prevent tumor insurgence and malignant disease.
    Frontiers in Oncology 07/2014; 4:131. DOI:10.3389/fonc.2014.00131
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    • "It was recently demonstrated that common myeloid and granulocyte progenitor populations also have angiogenic properties [39]. Myeloid cells participate in physiological angiogenesis and in pathological processes [38,40-42], and in the cancer field, different myeloid cell populations have been shown to regulate tumor angiogenesis [43]. "
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    Stem Cell Research & Therapy 04/2014; 5(2):50. DOI:10.1186/scrt438 · 3.37 Impact Factor
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    • "Traditionally, it was thought that ECs respond to VEGF during the angiogenic response and produce very little or undetectable amounts of VEGF (Kerbel, 2008). In other studies, using large, established tumors that are densely infiltrated by " activated " myeloid cells, it was shown that VEGF mainly originates from such myeloid cells and it controls tumor angiogenesis (reviewed in Apte and Voronov, 2008; Murdoch et al., 2008; Coffelt et al., 2010; Ferrara, 2010a; Mantovani and Sica, 2010; Qian and Pollard, 2010; Ruffell et al., 2010; Allavena and Mantovani, 2012; Gabrilovich et al., 2012). In the early stages of tumor development, as assessed in our studies, myeloid cells are probably not yet sufficiently activated to produce VEGF. "
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    Frontiers in Physiology 03/2014; 5:114. DOI:10.3389/fphys.2014.00114 · 3.53 Impact Factor
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