Connective tissue growth factor differentially binds to members of the cystine knot superfamily and potentiates platelet-derived growth factor-B signaling in rabbit corneal fibroblast cells

Pi, Liya; Chung, Pei-Yu; Sriram, Sriniwas; Rahman, Masmudur M.; Song, Wenlei; Scott, Edward W.; Petersen, Bryon E.; Schultz, Gregory S.

doi:10.4331/wjbc.v6.i4.379

Cited by 5 publications

(2 citation statements)

References 24 publications

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“…Importantly, these data also provide insights into the non-canonical mechanisms of PDGFRA activation. Although the classical ligands for PDGFRs are members of PDGF family, other ligands for these receptors such as VEGF-A 45 and CTGF 46 have been identified. Therefore, Endocan may serve an additional PDGFR ligand allowing cancer cells to activate PDGFRA signaling pathway, even if PDGFs are absent or diminished Somewhat surprisingly, our results demonstrated that Endocan itself or microenvironmental conditions formed in vivo in the presence or absence of Endocan induce highly stable phenotypic alterations of GBM cells that persist even after months of cultivation in identical conditions.…”

Section: Discussionmentioning

confidence: 99%

Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma

Bastola

Ghochani³

et al. 2020

Preprint

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Glioblastoma is a lethal brain cancer with active infiltration of tumor cells at the periphery where the vascular supply is enriched to create its own niche. Given that tumor recurrence is predominantly local, most of the seeds for lethal recurrence are hidden at the tumor edge and are surgically inaccessible. Here, we found that the spatial identity of the edge-located glioblastoma cells is, in the tested models, constructed by inter-cellular signals derived from the soluble factor endocan (protein product of Esm1) that is secreted by tumor-associated vascular endothelial (VE) cells. Injection of two distinct mouse glioblastoma models into Esm1 knockout (KO) mice resulted in tumors that failed to form typical edge lesions, resulting in the formation of compact core-only lesions. In sharp contrast, tumors derived in WT (Esm1-intact) mice harbored both tumor core and edge structures. Despite these obvious phenotypic differences, the aggressiveness of these two tumor types was indistinguishable in vivo. Surprisingly, regardless of the host system, co-injection of mixture of these two tumor subpopulations gave rise tumors with much worse survival, indicating that the accumulating tumor cell heterogeneity contributes to elevate malignancy. Mechanistically, endocan competes with PDGF to bind and activate PDGFRα in human glioblastoma cells, accompanied with the upregulation of the Myc transcriptional activity via alterations in its promoter chromatin structure. One of the mainstays of glioblastoma treatment, radiation, induces endocan secretion from VE cells, which promotes the radioresistance of the edge-located glioblastoma cells, allowing for the persistence of the edge structure. Collectively, these data suggest that intra-tumoral spatial heterogeneity is initiated by the VE cell-derived endocan signals through PDGFRα to construct tumor edge-to-core (E-to-C) architecture to cause lethal tumor recurrence.

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Section: Discussionmentioning

confidence: 99%

Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma

Bastola

Ghochani³

et al. 2020

Preprint

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“…Typically, CTGF and PDGFβ are both increased in fibrosis models and are consider profibrotic agents (35,37). Thus, it is possible that the alteration in PDGFβ is a compensatory effect based on its weak association with CTGF and not a therapeutic effect (38). …”

Section: Discussionmentioning

confidence: 99%

Connective Tissue Growth Factor Is a Novel Prodepressant

Turner

Sharma

Hagenauer

et al. 2018

Biological Psychiatry

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BACKGROUND: While downregulation of several growth factors in major depressive disorder is well established, less attention has been paid to the upregulation of other growth factors. Yet, upregulated growth factors may offer better therapeutic targets. We show that connective tissue growth factor (CTGF) represents a target based on its upregulation in major depressive disorder and studies in animal models implicating it in negative affect. METHODS: CTGF gene expression was first evaluated in the postmortem human amygdala. The findings were followed up in outbred rats and in two rat lines that were selectively bred for differences in novelty-seeking and anxiety behavior (bred low responders and bred high responders). We studied the impact of social defeat and early-life treatment with fibroblast growth factor 2 on CTGF expression. Finally, we assessed the ability of an anti-CTGF antibody (FG-3019) to alter CTGF expression and emotionality. RESULTS: In the human amygdala, CTGF expression was significantly increased in major depressive disorder compared with control subjects. CTGF expression was also significantly increased in the dentate gyrus of adult bred low responders compared with bred high responders. Social defeat stress in bred low responders significantly increased CTGF expression in the dentate gyrus. Early-life fibroblast growth factor 2, a treatment that reduces anxiety-like behavior throughout life, decreased CTGF expression in the adult dentate gyrus. In outbred rats, CTGF administration increased depression-like behavior. Chronic treatment with FG-3019 decreased CTGF expression, and acute and chronic treatment was antidepressant. CONCLUSIONS: This study is the first to implicate CTGF as a prodepressant molecule that could serve as a target for the development of novel therapeutics.

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A Reassessment of the Pathophysiology of Progressive Cardiorenal Disorders

Ré

2017

Medical Clinics of North America

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Connective tissue growth factor differentially binds to members of the cystine knot superfamily and potentiates platelet-derived growth factor-B signaling in rabbit corneal fibroblast cells

Cited by 5 publications

References 24 publications

Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma

Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma

Connective Tissue Growth Factor Is a Novel Prodepressant

A Reassessment of the Pathophysiology of Progressive Cardiorenal Disorders

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