Therapeutic Targeting of Tumor Growth and Angiogenesis with a Novel Anti-S100A4 Monoclonal Antibody

Hernández, José Luís; Padilla, Laura; Dakhel, Sheila; Coll, Toni; Hervás, Rubén; Adán, Jaume; Masa, Marc; Mitjans, Francesc; Martínez, Josep M.; Coma, Sílvia; Rodrı̀guez, Laura; Noé, Verónique; Ciudad, Carlos J.; Blasco, Francesc; Messeguer, Ramón

doi:10.1371/journal.pone.0072480

Cited by 80 publications

(86 citation statements)

References 56 publications

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“…[35][36][37] Because to the identification of VEGF overexpression as a marker for RNV, we examined the expression level of this protein in mouse retinas from four groups and found its expression to be increased in the OIR mouse model and decreased in the OIR mouse model treated with Ad-S100A4-RNAi. This finding was consistent with those of Jose et al, 38 who reported that the exogenous addition of recombinant S100A4 increased cell migration by acting synergistically with VEGF. Therefore, we speculated that the silencing of the S100A4 gene may reduce VEGF expression at both the protein and mRNA levels.…”

Section: Discussionsupporting

confidence: 93%

Silencing of S100A4, a metastasis-associated protein, inhibits retinal neovascularization via the downregulation of BDNF in oxygen-induced ischaemic retinopathy

Cheng

Xing

2016

Eye

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Background To investigate the underlying mechanism of S100A4 function and whether it has a role in retinal neovascularization (RNV) in a mouse model of oxygen-induced retinopathy (OIR). Methods Retinas from a mouse model of OIR were treated with and without an intravitreous injection of adenoviral-S100A4-RNAi or adenoviral green fluorescence protein (GFP) at postnatal day 12 (P12). At P17, the efficacy of adenoviral gene transfer was assessed using fluorescence microscopy and western blot analysis. RNV was evaluated by wholemount immunofluorescence staining of the mouse retina and by counting the number of pre-retinal neovascular cells. Protein and mRNA expression levels of S100A4, brainderived growth factor (BDNF), and vascular endothelial growth factor (VEGF) were measured using western blot analysis and real-time PCR. Results Retinal S100A4 levels were positively correlated with the progression of RNV. In the OIR-S100A4-RNAi group, both protein and mRNA expression levels of S100A4 in the retina significantly decreased at P17 compared with those in the OIR group. Ad-S100A4-RNAi transfer was clearly demonstrated by GFP fluorescence in many layers of the retina 5 days after the Ad-S100A4-RNAi transfer. Whole-mount immunofluorescence staining of the retina and quantification of the pre-retinal neovascular cells demonstrated that RNV was significantly inhibited. Meanwhile, the levels of the transcription and translation of BDNF,

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Section: Discussionsupporting

confidence: 93%

Silencing of S100A4, a metastasis-associated protein, inhibits retinal neovascularization via the downregulation of BDNF in oxygen-induced ischaemic retinopathy

Cheng

Xing

2016

Eye

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“…Indeed, it has been demonstrated that S100A4 synergizes with vascular endothelial growth factor (VEGF), via the RAGE receptor, in promoting endothelial cell migration and MMP-9 and MMP-13 gene expression. For this reason S100A4 protein is today included into the catalogue of putative terapeutic target [169].…”

Section: Sporadic S100 Proteinsmentioning

confidence: 99%

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

Pucci‐Minafra¹,

Cara²,

Musso³

et al. 2017

Preprint

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Abstract:The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The fragments were selected from patients with invasive ductal carcinoma of the breast, the most common and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers, useful for diagnostic and prognostic categorization of patients, in assessing postsurgical therapeutic regimes. The proteomic screening, by 2D-IPG and mass spectrometry, allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients, and proteins expressed sporadically among the same patients. Within the group of ubiquitous proteins, glycolytic enzymes and proteins with anti-apoptotic activity were predominant. Among the sporadic ones, proteins involved in cell motility, molecular chaperones and proteins involved in the detoxification appeared prevalent. The data of the present study indicates that the primary tumor growth is generally supported by two concurrent pathways: the inhibition of apoptosis and the stimulation of cellular proliferation. The second phase of the evolution of the tumor can be prematurely scheduled by the occasional presence of proteins involved in cell motility and in the defenses of the oxidative stress. To our knowledge this report on large-scales proteomics of breast cancer is currently a unique approach in the literature that offers the opportunity to evaluate the presence and recurrence of proteins to be used as prognostic indicators and susceptibility to metastasis in patients operated on for invasive ductal carcinoma of the breast.

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“…S100A4 was secreted by both tumor and stromal cells in melanoma xenograft model and supported (via RAGE) tumorigenesis and angiogenesis synergizing with vascular endothelial growth factor (VEGF) and also promoting endothelial cell migration by increasing MMP-9 activity. Endothelial cell migration, tumor growth and angiogenesis could have been abolished in this mode by the administration of anti-S100A4 monoclonal antibody 53 . S100A4 increased cell migration and invasion also in colon cancer cells and this effect may have been counteracted by soluble RAGE and anti-RAGE antibodies 54 .…”

Section: S100 Proteins and Cancermentioning

confidence: 99%

HMGB1, S100 proteins and other RAGE ligands in cancer - markers, mediators and putative therapeutic targets

et al. 2016

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Background and Aims. Activation of RAGE due to its increased expression in cancer cells or its stimulation by multiple ligands (AGEs, HMGB1, S100 proteins, etc.) may contribute to the proliferation, invasiveness of tumor cells and formation of distant metastases and also to the resistance of cancer to treatment. RAGE ligands could thus become both useful markers of disease severity and its outcome and, a potential therapeutic target. Conclusions. Better understanding of the role of RAGE activation in different types of cancer may help to define the role of ligand/RAGE antagonists as promising cancer treatment.

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Therapeutic Targeting of Tumor Growth and Angiogenesis with a Novel Anti-S100A4 Monoclonal Antibody

Cited by 80 publications

References 56 publications

Silencing of S100A4, a metastasis-associated protein, inhibits retinal neovascularization via the downregulation of BDNF in oxygen-induced ischaemic retinopathy

Silencing of S100A4, a metastasis-associated protein, inhibits retinal neovascularization via the downregulation of BDNF in oxygen-induced ischaemic retinopathy

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

HMGB1, S100 proteins and other RAGE ligands in cancer - markers, mediators and putative therapeutic targets

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