The placental growth factor as a target against hepatocellular carcinoma in a diethylnitrosamine-induced mouse model

Heindryckx, Femke; Coulon, S.; Terrie, Ellen; Casteleyn, Christophe; Stassen, Jean–Marie; Geerts, Anja; Libbrecht, Louis; Allemeersch, Joke; Carmeliet, Peter; Colle, Isabelle; Vlierberghe, Hans Van

doi:10.1016/j.jhep.2012.09.032

Cited by 26 publications

(27 citation statements)

References 41 publications

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“…Consistent with this notion, PlGF has been shown to promote monocyte infiltration in ischemic tissues, tumors, atherosclerotic plaques, and bone fractures (18, 37). Moreover, prior studies have demonstrated that inhibition of PlGF might also affect tumors by reducing TAM infiltration (18, 22–26). It also induces polarization of TAM to an M2-like proangiogenic phenotype, thereby promoting tumor vessel disorganization (17, 18, 38).…”

Section: Discussionmentioning

confidence: 99%

“…It is noteworthy that PlGF is dispensable for development and health, while blockage of PlGF pathway has been shown to reduce pathological angiogenesis without affecting healthy blood vessels (17, 18, 21). Recent reports have demonstrated that PlGF is overexpressed in cirrhotic liver and hepatocellular carcinoma (HCC) both in human and in rodent models (18, 22–26). Furthermore, we and others previously have shown that blockade of PlGF by specific antibody, small interfering RNA (siRNA), or genetic ablation suppressed liver fibrogenesis (22, 23), reduced portal hypertension (24) and inhibited HCC (18, 25, 26).…”

Section: Introductionmentioning

confidence: 99%

“…Recent reports have demonstrated that PlGF is overexpressed in cirrhotic liver and hepatocellular carcinoma (HCC) both in human and in rodent models (18, 22–26). Furthermore, we and others previously have shown that blockade of PlGF by specific antibody, small interfering RNA (siRNA), or genetic ablation suppressed liver fibrogenesis (22, 23), reduced portal hypertension (24) and inhibited HCC (18, 25, 26). Thus, PlGF signaling represents a promising target for therapy of chronic liver disease with angiogenesis (17, 22–26).…”

Section: Introductionmentioning

confidence: 99%

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Placental Growth Factor Contributes to Liver Inflammation, Angiogenesis, Fibrosis in Mice by Promoting Hepatic Macrophage Recruitment and Activation

Jin

Yao

et al. 2017

Front. Immunol.

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Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, mediates wound healing and inflammatory responses, exerting an effect on liver fibrosis and angiogenesis; however, the precise mechanism remains unclear. The aims of this study are to identify the role of PlGF in liver inflammation and fibrosis induced by bile duct ligation (BDL) in mice and to reveal the underlying molecular mechanism. PlGF small interfering RNA (siRNA) or non-targeting control siRNA was injected by tail vein starting 2 days after BDL. Liver inflammation, fibrosis, angiogenesis, macrophage infiltration, and hepatic stellate cells (HSCs) activation were examined. Our results showed that PlGF was highly expressed in fibrotic livers and mainly distributed in activated HSCs and macrophages. Furthermore, PlGF silencing strongly reduced the severity of liver inflammation and fibrosis, and inhibited the activation of HSCs. Remarkably, PlGF silencing also attenuated BDL-induced hepatic angiogenesis, as evidenced by attenuated liver endothelial cell markers CD31 and von Willebrand factor immunostaining and genes or protein expression. Interestingly, these pathological ameliorations by PlGF silencing were due to a marked reduction in the numbers of intrahepatic F4/80+, CD68+, and Ly6C+ cell populations, which were reflected by a lower expression of these macrophage marker molecules in fibrotic livers. In addition, knockdown of PlGF by siRNA inhibited macrophages activation and substantially suppressed the expression of pro-inflammatory cytokines and chemokines in fibrotic livers. Mechanistically, evaluation of cultured RAW 264.7 cells revealed that VEGF receptor 1 (VEGFR1) mainly involved in mediating the role of PlGF in macrophages recruitment and activation, since using VEGFR1 neutralizing antibody blocking PlGF/VEGFR1 signaling axis significantly inhibited macrophages migration and inflammatory responses. Together, these findings indicate that PlGF plays an important role in liver inflammation, angiogenesis, and fibrosis by promoting hepatic macrophage recruitment and activation, and suggest that blockage of PlGF could be a promising novel therapy for chronic fibrotic liver diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Placental Growth Factor Contributes to Liver Inflammation, Angiogenesis, Fibrosis in Mice by Promoting Hepatic Macrophage Recruitment and Activation

Jin

Yao

et al. 2017

Front. Immunol.

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“…Heindryckx et al assessed inhibition of PlGF in mouse model for hepatocellular carcinoma (HCC). They observed a significantly decrease of tumor burden by inhibiting neovascularization, by decreasing hepatic macrophage recruitment and by normalizing the remaining bloods vessels, thereby decreasing hypoxia and reducing the prometastatic potential of HCC [22]. In a murine model of fibrosarcoma, PlGF showed important effects on vascular remodeling and normalization, altering tumor growth [23].…”

Section: Discussionmentioning

confidence: 99%

Circulating vascular endothelial growth factor (VEGF) as predictive factor of progression-free survival in patients with advanced chordoma receiving sorafenib: an analysis from a phase II trial of the french sarcoma group (GSF/GETO)

et al. 2016

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BackgroundPatients with advanced chordoma are often treated with tyrosine kinase inhibitors without any predictive factor to guide decision. We report herein an ancillary analysis of the the Angionext phase II trial (NCT 00874874).ResultsFrom May 2011 to January 2014, 26 were sampled. The 9-month PFS rate was 72.9% (95%-CI: 45.9-87.9). During sorafenib treatment, a significant increase in PlGF (18.4 vs 43.8 pg/mL, p<0.001) was noted along with a non-significant increase in VEGF (0.7 vs 1.0 ng/mL, p=0.07). VEGF at D1 >1.04 ng/mL (HR=12.5, 95%-CI: 1.37-114, p=0.025) and VEGF at D7 >1.36 ng/mL (HR=10.7, 95%-CI: 1.16-98, p=0.037) were associated with shorter PFS. The 9-month PFS rate was 92.3% (95%-CI: 56.6-98.9) when VEGF at D1 was ≤1.04 ng/mL versus 23.3% (95%-CI: 1.0-63.2) when >1.04 ng/mL.Patients and MethodsChordoma patients were treated with sorafenib 800 mg/day for 9 months, unless earlier occurrence of progression or toxicities. Six biomarkers (sE-Selectin, VEGF, VEGF-C, placental growth factor (PlGF), Thrombospondin, Stem Cell Factor (SCF)) were measured at baseline (day 1: D1) and day 7 (D7).ConclusionHigh levels of VEGF was associated with poor outcome.

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“…For rapid growth, tumor cells often secrete a large number of angiogenic growth factors including vascular endothelial growth factor (VEGF), placental growth factor (PIGF) and angiogenin [85,86]. These factors will promote the abnormal growth of tumor vessels that contribute to the formation of hypoxic microenvironment.…”

Section: Strategies For Correcting Hypoxia and Oxidative Stressmentioning

confidence: 99%

Novel Therapeutic Strategies for Solid Tumor Based on Body’s Intrinsic Antitumor Immune System

Duan

2018

Cell Physiol Biochem

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The accumulation of mutated somatic cells due to the incompetency of body’s immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumor-specific antigens (TSA) or TSA-sensitized dendritic cells (DC). Once initiated, specific anti-tumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced. Several strategies may enhance antitumor action of immune system, such as supplying tumor-targeted antibody, activating T cells, enhancing the activity and tumor recognition of NK cells, promoting tumor-targeted phagocytosis of macrophages, and eliminating the immunosuppressive myeloid-derived suppressor cells (MDSCs) and Treg cells. Apart from the immune system, the removal of tumor burden still needs to be assisted by drugs, surgery or radiation. And the body’s internal environment and tumor microenvironment should be improved to recover immune cell function and prevent tumor growth. Multiple microenvironment modulatory therapies may be applied, including addressing hypoxia and oxidative stress, correcting metabolic disorders, and controlling chronic inflammation. Finally, to cure tumor and prevent tumor recurrence, repairing or supporting therapy that consist of tissue repair and nutritional supplement should be applied properly.

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The placental growth factor as a target against hepatocellular carcinoma in a diethylnitrosamine-induced mouse model

Cited by 26 publications

References 41 publications

Placental Growth Factor Contributes to Liver Inflammation, Angiogenesis, Fibrosis in Mice by Promoting Hepatic Macrophage Recruitment and Activation

Placental Growth Factor Contributes to Liver Inflammation, Angiogenesis, Fibrosis in Mice by Promoting Hepatic Macrophage Recruitment and Activation

Circulating vascular endothelial growth factor (VEGF) as predictive factor of progression-free survival in patients with advanced chordoma receiving sorafenib: an analysis from a phase II trial of the french sarcoma group (GSF/GETO)

Novel Therapeutic Strategies for Solid Tumor Based on Body’s Intrinsic Antitumor Immune System

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