Proangiogenic Factor PlGF Programs CD11b+ Myelomonocytes in Breast Cancer during Differentiation of Their Hematopoietic Progenitors

A novel gene expression signature in peripheral blood mononuclear cells for early detection of colorectal cancer

“…11,12 Tumour-recruited BMDC are likely to initiate differentiation and effector programs during their mobilisation from the bone marrow, which might be detectable during their transition in the blood. 13,14 The report of signatures derived from peripheral blood mononuclear cells (PBMC) gene expression profiles and associated with breast, 15 renal, 16,17 pulmonary, 18 bladder 19 and digestive cancers 8,9,20 further corroborates these observations. The aim of this study was to demonstrate whether the feasibility of identifying gene expression signatures in PBMC was able to discriminate patients with AP and CRC from subjects without these lesions.…”

Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade

“…17,31 It has also been speculated that combing anti-angiogenic and immunotherapies may help to improve the therapeutic efficacy of either therapy used alone. 31,36,37 Here, we used the orthotopic and syngenic, highly angiogenic and metastatic 4T1 murine breast adenocarcinoma model, 38 well known to effectively mobilize CD11b C bone marrow-derived cells (BMDC), 38,39 including MDSC, 40,41 and to be immunogenic, [42][43][44] to monitor the effect of anti-angiogenic therapy on MDSC mobilization and activity in relationship to tumor growth and metastasis. We show that the anti-VEGFR-2 antibody DC101, 45 inhibits tumor angiogenesis, tumor growth, metastasis and partially reversed MDSC inhibitory activity on T cells, decreased the recruitment of Tregs at tumor and metastatic sites and enhanced Arg I expression.…”

PlGF: A Multitasking Cytokine with Disease-Restricted Activity

“…A possible implication of these findings is that PlGF blockade might inhibit disease processes more selectively than physiological homeostasis and thus evoke fewer side effects. We summarize below the findings on PlGF's (Foidart et al 2009;Furuya et al 2011) Heart PlGF-induced revascularization of ischemic myocardium and vessel enlargement in remote myocardium preserve cardiac performance following infarction (Luttun et al 2002;Kolakowski et al 2006;Roncal et al 2008) Knockout: impaired angiogenesis and inflammation in infarct border (Carmeliet et al 2001) Knockout: Normal exercise induces angiogenesis (Gigante et al 2004) Skeletal muscle PlGF protein or gene delivery: enhances angiogenesis, collateral growth, and blood flow in ischemic limb (Luttun et al 2002;Pipp et al 2003;Babiak et al 2004); restores microcirculation in aged dystrophic muscle (Gargioli et al 2008) Knockout: impaired collateral growth in ischemic limb (Carmeliet et al 2001;Scholz et al 2003;Gigante et al 2006) Knockout: normal exercise-induced angiogenesis (Gigante et al 2004) Eye PlGF prevents vessel obliteration in hyperoxia without including neovascularization (Shih et al 2003) Local ocular PlGF protein or gene transfer causes hematoretinal barrier breakdown and edema (Miyamoto et al 2007;Kowalczuk et al 2011) Knockout or aPlGF: impaired choroidal neovascularization (Carmeliet et al 2001;Rakic et al 2003;Van de Veire et al 2010) Knockout or aPlGF does not impair retinal vascularization during development (Carmeliet et al 2001;Feeney et al 2003 (Carmeliet et al 2001;Scholz et al 2003;Gigante et al 2006) (Eriksson et al 2002;Xu et al 2006;Schomber et al 2007;Tarallo et al 2010) PlGF educates CD34 þ progenitors to proangiogenic CD11b þ myelomonocytes in breast cancer (Laurent et al 2011...…”

“…PlGF also stimulates inflammatory cell recruitment and activation (Kerber et al 2008;Ding et al 2010;Van de Veire et al 2010;Laurent et al 2011). It also induces polarization of TAMs to an M2-like proangiogenic phenotype, thereby promoting tumor vessel disorganization (Rolny et al 2011).…”

“…Phenocopying the effects seen upon PlGF blockade by gene inactivation or RNA interference (Carmeliet et al 2001;Van de Veire et al 2010;Laurent et al 2011), pharmacological PlGF inhibition by neutralizing antibodies (anti-PlGF antibodies 5D11D4, 3C7A5) or by PlGF/FLT1 peptide antagonists reduced tumor growth, angiogenesis, lymphangiogenesis, inflammation, and metastasis in different ectopically and orthotopically implanted tumors in mouse models, in the absence of adverse side effects (Fischer et al 2007;Taylor and Goldenberg 2007;Coenegrachts et al 2010;Bagley et al 2011). PlGF is also diffusely expressed in medulloblastoma, the most common malignant brain tumor of childhood, and genetic and pharmacologic inhibition of PlGF leads to growth delay and regression of medulloblastoma models in mice as well (Snuderl et al 2010).…”