Insulin-like growth factor binding protein 7 exhibits tumor suppressive and vessel stabilization properties in U87MG and T98G glioblastoma cell lines

Pen, Ally; Durocher, Yves; Slinn, Jacqueline; Rukhlova, Marina; Charlebois, Claudie; Stanimirovic, Danica; Moreno, María

doi:10.4161/cbt.12.7.17171

Cited by 31 publications

(25 citation statements)

References 58 publications

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“…All three encode extracellular proteins, and have known effects on mesenchymal and smooth muscle differentiation. [73][74][75][76][77][78] Indeed, we saw that they have diverging effects on SMC number and SMC phenotype ( Figure 6E).…”

Section: Circadian Clock Gene Expression In Stretch and Obstructionmentioning

confidence: 82%

Persistent myopathy despite release of partial obstruction: in vivo reversal of dysfunction and transcriptional responses using rapamycin

et al. 2020

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Current and potential medical therapy for obstruction‐induced myopathic bladder dysfunction (from benign prostatic hyperplasia or posterior urethral valves) focuses on symptoms. The persistent tissue pathology and dysfunction after release of obstruction is often deemed irreversible without any systematic therapeutic approaches. As rapamycin can attenuate bladder smooth muscle hypertrophy and dysfunction during the genesis of partial obstruction in vivo, we tested whether rapamycin could improve persistent function after release of obstruction (de‐obstruction or REL). Female Sprague‐Dawley rat bladders were partially obstructed (PBO) by suturing around both the urethra and a para‐urethral steel rod, then removing the rod. One day prior to release of obstruction (preREL), voiding parameters and residual urine volume of preREL+future rapa, preREL+future veh groups were recorded. Release of obstruction (REL) was performed by suture removal following 6 weeks of PBO. For 4 more weeks after the de‐obstruction, REL animals were randomized to rapamycin (REL+rapa) or vehicle (REL+veh). PBO for 6 weeks were used as positive controls. In shams, the urethra was exposed, but no suture tied. Voiding parameters and residual urine volume were measured prior to sacrifice of sham and REL+veh or REL+rapa, and PBO. Rapamycin efficacy was tested by pair‐wise comparison of changes in individual voiding data from preREL+future veh or preREL+future rapa versus REL+veh or REL+rapa, respectively, as well as by comparisons of REL+veh to REL+rapa groups. Bladders were weighed and processed for a high‐throughput QPCR array, and histopathology. Bladder/body mass ratios with PBO increased significantly and remained higher in the release phase in REL+veh animals. REL+rapa versus REL+veh improved residual volumes and micturition fractions toward sham levels. Three genes encoding extracellular proteins, BMP2, SOD3, and IGFBP7, correlated with functional improvement by Pearson's correlations. The promoters of these genes showed enrichment for several motifs including circadian E‐boxes. While obstruction and REL augmented CLOCK and NPAS2 expression above sham levels, rapamycin treatment during release significantly blocked their expression. This experimental design of pharmaco‐intervention during the de‐obstruction phase revealed a novel pathway dysregulated during the clinically relevant treatment phase of obstructive bladder myopathy.

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Section: Circadian Clock Gene Expression In Stretch and Obstructionmentioning

confidence: 82%

Persistent myopathy despite release of partial obstruction: in vivo reversal of dysfunction and transcriptional responses using rapamycin

et al. 2020

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“…Similar to studies with tracheal and brain matrices, and through proteomics analysis, the current study revealed the presence of several residual growth factors in the kidney and lung scaffolds that may be beneficial in scaffold recellularization. Insulin-like growth factor binding protein-7, which plays a role in cellular proliferation and vessel stabilization [16], was detected in the kidney scaffold. In addition, both kidney and lung scaffolds contained EGF-7 precursor, which plays a role in vascular tubulogenesis and protects endothelial cells from hypoxia-induced apoptosis [17].…”

Section: Discussionmentioning

confidence: 99%

Tissue Specificity of Decellularized Rhesus Monkey Kidney and Lung Scaffolds

et al. 2013

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Initial steps in establishing an optimal strategy for functional bioengineered tissues is generation of three-dimensional constructs containing cells with the appropriate organization and phenotype. To effectively utilize rhesus monkey decellularized kidney scaffolds, these studies evaluated two key parameters: (1) residual scaffold components after decellularization including proteomics analysis, and (2) the use of undifferentiated human embryonic stem cells (hESCs) for recellularization in order to explore cellular differentiation in a tissue-specific manner. Sections of kidney and lung were selected for a comparative evaluation because of their similar pattern of organogenesis. Proteomics analysis revealed the presence of growth factors and antimicrobial proteins as well as stress proteins and complement components. Immunohistochemistry of recellularized kidney scaffolds showed the generation of Cytokeratin+ epithelial tubule phenotypes throughout the scaffold that demonstrated a statistically significant increase in expression of kidney-associated genes compared to baseline hESC gene expression. Recellularization of lung scaffolds showed that cells lined the alveolar spaces and demonstrated statistically significant upregulation of key lung-associated genes. However, overall expression of kidney and lung-associated markers was not statistically different when the kidney and lung recellularized scaffolds were compared. These results suggest that decellularized scaffolds have an intrinsic spatial ability to influence hESC differentiation by physically shaping cells into tissue-appropriate structures and phenotypes, and that additional approaches may be needed to ensure consistent recellularization throughout the matrix.

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“…31 Intravenous recombinant IGFBP7 treatment has shown good tumour-suppressive effects in mouse models of several cancers, including glioblastoma. 28,32 The potential anticancer effects of IGFBP7 in glioma therefore warrant further investigation.…”

Section: Discussionmentioning

confidence: 99%

Low expression of insulin-like growth factor binding protein 7 associated with poor prognosis in human glioma

et al. 2014

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Objectives: To investigate insulin-like growth factor binding protein 7 (IGFBP7) mRNA levels in human glioma and normal brain tissue, and to determine their clinical significance. Methods: In this retrospective study, IGFBP7 mRNA was quantified by real-time reverse transcription-polymerase chain reaction in brain tissue samples from patients with glioma and normal control subjects. Kaplan-Meier and Cox proportional hazards analyses were performed to determine any clinical and prognostic associations. Results: IGFBP7 mRNA levels were significantly lower in glioma tissue (n ¼ 120) than in normal brain tissue (n ¼ 20). Low (i.e. below the median, 5.9) IGFBP7 mRNA levels were significantly associated with larger tumour size (!5 cm, compared with <5 cm, diameter). Patients with high (above median) IGFBP7 had longer overall survival than those with low IGFBP7. Tumour grade and IGFBP7 mRNA level were independent predictors of overall survival. Conclusions: IGFBP7 downregulation is associated with poor prognosis in glioma, and this molecule may represent both a prognostic marker and a potential therapeutic target.

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Insulin-like growth factor binding protein 7 exhibits tumor suppressive and vessel stabilization properties in U87MG and T98G glioblastoma cell lines

Cited by 31 publications

References 58 publications

Persistent myopathy despite release of partial obstruction: in vivo reversal of dysfunction and transcriptional responses using rapamycin

Persistent myopathy despite release of partial obstruction: in vivo reversal of dysfunction and transcriptional responses using rapamycin

Tissue Specificity of Decellularized Rhesus Monkey Kidney and Lung Scaffolds

Low expression of insulin-like growth factor binding protein 7 associated with poor prognosis in human glioma

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