Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression

Brassart‐Pasco, Sylvie; Brézillon, Stéphane; Brassart, Bertrand; Ramont, Laurent; Oudart, Jean‐Baptiste; Monboisse, Jean-Claude

doi:10.3389/fonc.2020.00397

Cited by 200 publications

(171 citation statements)

References 163 publications

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“…The NC1 domains of the different α(IV) collagen chains were reported to exert anti-tumor or anti-angiogenic effects (Mundel and Kalluri, 2007;Monboisse et al, 2014;Brassart-Pasco et al, 2020). We and others demonstrated that the anti-tumor activities of Tumstatin or Tetrastatin were mediated through binding to α v β 3 integrin at the tumor cell surface (Pasco et al, 2000;Brassart-Pasco et al, 2012;Lambert et al, 2018).…”

Section: Discussionmentioning

confidence: 97%

Angiogenesis Inhibition by a Short 13 Amino Acid Peptide Sequence of Tetrastatin, the α4(IV) NC1 Domain of Collagen IV

Vautrin-Glabik

Devy

Bour

et al. 2020

Front. Cell Dev. Biol.

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Angiogenesis is defined as the formation of new capillaries by sprouting from the pre-existing microvasculature. It occurs in physiological and pathological processes particularly in tumor growth and metastasis. α1, α2, α3, and α6 NC1 domains from type IV collagen were reported to inhibit tumor angiogenesis. We previously demonstrated that the α4 NC1 domain from type IV collagen, named Tetrastatin, inhibited tumor growth in a mouse melanoma model. The inhibitory activity was located in a 13 amino acid sequence named QS-13. In the present paper, we demonstrate that QS-13 decreases VEGF-induced-angiogenesis in vivo using the Matrigel plug model. Fluorescence molecular tomography allows the measurement of a 65% decrease in Matrigel plug angiogenesis following QS-13 administration. The results are confirmed by CD31 microvessel density analysis on Matrigel plug slices. QS-13 peptide decreases Human Umbilical Vein Endothelial Cells (HUVEC) migration and pseudotube formation in vitro. Relevant QS-13 conformations were obtained from molecular dynamics simulations and docking. A putative interaction of QS-13 with α 5 β 1 integrin was investigated. The interaction was confirmed by affinity chromatography, solid phase assay, and surface plasmon resonance. QS-13 binding site on α 5 β 1 integrin is located in close vicinity to the RGD binding site, as demonstrated by competition assays. Collectively, our results suggest that QS-13 exhibits a mighty anti-angiogenic activity that could be used in cancer treatment and other pathologies with excessive angiogenesis such as hemangioma, psoriasis or diabetes.

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Section: Discussionmentioning

confidence: 97%

Angiogenesis Inhibition by a Short 13 Amino Acid Peptide Sequence of Tetrastatin, the α4(IV) NC1 Domain of Collagen IV

Vautrin-Glabik

Devy

Bour

et al. 2020

Front. Cell Dev. Biol.

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“…Collagens play structural roles in the mechanical properties of tissues and can interact with cells via several receptor families to regulate cell proliferation, migration, and differentiation [49] . Enrichment analysis revealed that these genes in Module 1 were enriched in many cancer-related pathways, including focal adhesion [50] , the PI3K-Akt signaling pathway [47] , collagen degradation [51] , and pathways in cancer. We also found that MeDEGs in Module 2 were related to the immune system, chemokine signaling pathway, and signaling by interleukins.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of DNA methylation and gene expression profiles in rectal cancer

Zhang¹,

Meng²,

Chao³

et al. 2020

Preprint

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BackgroundAbnormal hypomethylation of oncogenes and hypermethylation of tumor suppressor genes play important roles in human tumorigenesis and cancer progression, including those of rectal cancer (RC). However, conjoint analysis of RC involving both gene expression and methylation profiling datasets remains rare. This study aimed to identify methylation-regulated differentially expressed genes (MeDEGs) and to evaluate their prognostic value in RC through bioinformatics analysis.MethodsGene expression (GSE20842 and GSE68204) and gene methylation (GSE75546) profiling datasets were obtained from the Gene Expression Omnibus database. GEO2R was adopted to identify differentially expressed genes (DEGs) and differentially methylated genes (DMGs). MeDEGs were obtained by overlapping the DEGs and DMGs and then subjected to protein–protein interaction (PPI) network analysis using STRING. Modules and hub genes within the network were identified using MCODE and CytoHubba, respectively. Prognostic MeDEGs were selected by univariate Cox regression. Finally, our findings were validated based on The Cancer Genome Atlas (TCGA) database.ResultsIn total, 243 upregulated-hypomethylated and 51 downregulated-hypermethylated genes were identified as MeDEGs. A PPI network of MeDEGs was constructed with 290 nodes and 578 edges. Three modules and three hub genes—COL3A1, FPR1, and PLK1—within the network were identified. Three MeDEGs—NFE2, COMP, and LAMA1—were found to be survival-related. Furthermore, the expression and methylation status of two hub genes (excluding FPR1) and the three prognostic MeDEGs were also significantly altered in TCGA and were consistent with our findings.ConclusionsWe identified novel MeDEGs and explored their relationship with survival in RC. Our methodology may provide an effective bioinformatics basis for further understanding of the methylation-mediated regulatory mechanisms in RC.

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“…The GSEA revealed that the terms cytokine-cytokine receptor interaction, ECM-related, adhesion receptor interaction, cell adhesion molecules cams, focal adhesion, and immune cell related pathways were signi cantly enriched in IGFBP7 high expression phenotype. It has been reported that ECM components such as collagen, broblasts and their associated signaling molecules contribute to tumor cell proliferation, migration and invasion in various cancers [40,41]. Moreover, IGFBP7 has been reported to regulate epithelial-mesenchylmal transition (EMT) in some solid tumors [12,42,43].…”

Section: Discussionmentioning

confidence: 99%

Increased IGFBP7 Expression Correlates with Poor Prognosis and Immune Infiltration in Gastric Cancer: An Integrated Bioinformatics Analysis

Qi¹,

Zhao²,

Song³

et al. 2020

Preprint

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Background Insulin-like growth factor binding protein-7 (IGFBP7) contributes to multiple biological processes in various tumors. However, the role of IGFBP7 in gastric cancer (GC) is still undetermined. The study aims to explore the role of IGFBP7 in GC via an integrated bioinformatics analysis.Methods IGFBP7 expression levels in GC and its normal gastric tissues were analyzed using multiple databases, including the Tumor Immune Estimation Resource (TIMER), Oncomine, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The methylation analysis was conducted with MEXPRESS, UALCAN and Xena online tools. The survival analysis was conducted using the Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Coexpressed genes of IGFBP7 were selected with the cBioPortal tool and enrichment analysis was conducted with the clusterProfiler package in R software. Gene set enrichment analysis (GSEA) was performed to explore the IGFBP7-related biological processes involved in GC. Correlations between IGFBP7 and immune cell infiltrates were analyzed using the TIMER database.Results IGFBP7 expression was significantly upregulated in GC and correlated with stage, grade, tumor status and Helicobacter pylori infection. High IGFBP7 expression and low IGFBP7 methylation levels were significantly associated with short survival of patients with GC. Univariate and multivariate analyses revealed that IGFBP7 was an independent risk factor for GC. The coexpressed genes LHFPL6, SEPTIN4, HSPB2, LAYN and GGT5 predicted unfavorable outcomes of GC. Enrichment analysis showed that the coexpressed genes were involved in extracellular matrix (ECM)-related processes. GSEA indicated that IGFBP7 was positively related to ECM and inflammation-related pathways. TIMER analysis indicated that the IGFBP7 expression level was strongly correlated with genes related to various infiltrating immune cells in GC, especially with gene markers of tumor associated macrophages (TAMs).Conclusions We demonstrate that increased IGFBP7 expression correlates with poor prognosis and immune cell infiltration in GC. IGFBP7 might be a potential biomarker for the diagnosis and targeted therapy for GC.

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Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression

Cited by 200 publications

References 163 publications

Angiogenesis Inhibition by a Short 13 Amino Acid Peptide Sequence of Tetrastatin, the α4(IV) NC1 Domain of Collagen IV

Angiogenesis Inhibition by a Short 13 Amino Acid Peptide Sequence of Tetrastatin, the α4(IV) NC1 Domain of Collagen IV

Comprehensive analysis of DNA methylation and gene expression profiles in rectal cancer

Increased IGFBP7 Expression Correlates with Poor Prognosis and Immune Infiltration in Gastric Cancer: An Integrated Bioinformatics Analysis

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