ProNGF Expression and Targeting in Glioblastoma Multiforme

Marsland, Mark; Dowdell, Amiee; Faulkner, Sam; Jobling, Phillip; Rush, Robert A.; Gedye, Craig; Griffin, Cassandra; Baker, Mark A.; Marsland, Joanne; Jiang, Chen Chen; Hondermarck, Hubert

doi:10.3390/ijms24021616

Cited by 5 publications

(6 citation statements)

References 41 publications

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“…The NGF is the product of a single gene on chromosome 1. Tropomyosin-related kinase (Trk) receptors have a high affinity for the NGF [21]. Through the TrkA receptor, the NGF regulates neuronal cell survival and differentiation and axonal and dendritic growth.…”

Section: The Ngf's Receptors and Its Effect On Neuronsmentioning

confidence: 99%

The Crosstalk between Nerves and Cancer—A Poorly Understood Phenomenon and New Possibilities

Benzaquen,

Lawrence,

Taussky

et al. 2024

Cancers

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Introduction: Crosstalk occurs between nerve and cancer cells. These interactions are important for cancer homeostasis and metabolism. Nerve cells influence the tumor microenvironment (TME) and participate in metastasis through neurogenesis, neural extension, and axonogenesis. We summarized the past and current literature on the interaction between nerves and cancer, with a special focus on pancreatic ductal adenocarcinoma (PDAC), prostate cancer (PCa), and the role of the nerve growth factor (NGF) in cancer. Materials/Methods: We reviewed PubMed and Google Scholar for the relevant literature on the relationship between nerves, neurotrophins, and cancer in general and specifically for both PCa and PDAC. Results: The NGF helped sustain cancer cell proliferation and evade immune defense. It is a neuropeptide involved in neurogenic inflammation through the activation of several cells of the immune system by several proinflammatory cytokines. Both PCa and PDAC employ different strategies to evade immune defense. The prostate is richly innervated by both the sympathetic and parasympathetic nerves, which helps in both growth control and homeostasis. Newly formed autonomic nerve fibers grow into cancer cells and contribute to cancer initiation and progression through the activation of β-adrenergic and muscarinic cholinergic signaling. Surgical or chemical sympathectomy prevents the development of prostate cancer. Beta-blockers have a high therapeutic potential for cancer, although current clinical data have been contradictory. With a better understanding of the beta-receptors, one could identify specific receptors that could have an effect on prostate cancer development or act as therapeutic agents. Conclusion: The bidirectional crosstalk between the nervous system and cancer cells has emerged as a crucial regulator of cancer and its microenvironment. Denervation has been shown to be promising in vitro and in animal models. Additionally, there is a potential relationship between cancer and psychosocial biology through neurotransmitters and neurotrophins.

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Section: The Ngf's Receptors and Its Effect On Neuronsmentioning

confidence: 99%

The Crosstalk between Nerves and Cancer—A Poorly Understood Phenomenon and New Possibilities

Benzaquen,

Lawrence,

Taussky

et al. 2024

Cancers

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“…FFPE tissue sections of 4 µm were processed for sortilin immunohistochemical detection as previously described [19]. Sections were labelled with anti-sortilin (0.8 mg/mL, catalogue number ANT-009, Alomone labs, Jerusalem, Israel) followed by a secondary antibody (catalogue number MP-7401, Vector Laboratories, Newark, CA, USA).…”

Section: Immunohistochemical Detection and Quantification Of Sortilin...mentioning

confidence: 99%

“…Following IHC, slides were digitized using the Aperio AT2 scanner (Leica Biosystems, Wetzlar, Germany) at 40× absolute resolution. Quantification of sortilin immunohistological staining intensities was performed using the HALOTM image analysis platform (version 3.3, Indica Labs, Albuquerque, NM, USA), as reported [19].…”

Section: Immunohistochemical Detection and Quantification Of Sortilin...mentioning

confidence: 99%

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The Membrane Protein Sortilin Is a Potential Biomarker and Target for Glioblastoma

Marsland

Dowdell

Faulkner

et al. 2023

Cancers

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Glioblastoma (GBM) is a devastating brain cancer with no effective treatment, and there is an urgent need for developing innovative biomarkers as well as therapeutic targets for better management of the disease. The membrane protein sortilin has recently been shown to participate in tumor cell invasiveness in several cancers, but its involvement and clinical relevance in GBM is unclear. In the present study, we explored the expression of sortilin and its potential as a clinical biomarker and therapeutic target for GBM. Sortilin expression was investigated by immunohistochemistry and digital quantification in a series of 71 clinical cases of invasive GBM vs. 20 non-invasive gliomas. Sortilin was overexpressed in GBM and, importantly, higher expression levels were associated with worse patient survival, pointing to sortilin tissue expression as a potential prognostic biomarker for GBM. Sortilin was also detectable in the plasma of GBM patients by enzyme-linked immunosorbent assay (ELISA), but no differences were observed between sortilin levels in the blood of GBM vs. glioma patients. In vitro, sortilin was detected in 11 brain-cancer-patient-derived cell lines at the anticipated molecular weight of 100 kDa. Interestingly, targeting sortilin with the orally bioavailable small molecule inhibitor AF38469 resulted in decreased GBM invasiveness, but cancer cell proliferation was not affected, showing that sortilin is targetable in GBM. Together, these data suggest the clinical relevance for sortilin in GBM and support further investigation of GBM as a clinical biomarker and therapeutic target.

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“…It can be diagnosed by a variety of techniques such as positron emission tomography, computed tomography, and magnetic resonance imaging 2 . At present, the treatment method of GBM is mainly surgery, supplemented by chemoradiotherapy with the standards chemotherapy drug temozolomide 3 , 4 . However, due to the heterogeneity and complexity of tumor cells, high local aggressiveness and prominent neovascularization, patients with GBM have a poor prognosis 5 , 6 .…”

Section: Introductionmentioning

confidence: 99%

NCDN is a Potential Biomarker and Therapeutic Target for Glioblastoma

Huang,

Xu,

Dai

et al. 2024

J. Cancer

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Background: Glioblastoma (GBM) is a type of central nervous system malignancy. In our study, we determined the effect of NCDN in GBM patients through The Cancer Genome Atlas (TCGA) data analysis, and studied the effects of NCDN on GBM cell function to estimate its potential as a therapeutic target. Methods: Gene expression profiles of glioblastoma cohort were acquired from TCGA database and analyzed to look for central genes that may serve as GBM therapeutic targets. Then the cell function of NCDN in glioblastoma cell was explored through in vitro cell experiments. Results: Through gene ontology (GO) analysis, weighted gene co-expression network analysis (WGCNA), and survival analysis, we identified three key genes ( NCDN , PAK1 and SPRYD3 ) associated with poor prognosis in glioblastoma. In vitro experiments showed impaired cell migration, apoptosis, and cell cycle arrest in NCDN knockdown cells. Conclusion: NCDN affects the progress and prognosis of glioblastoma by promoting cell migration and inhibiting apoptosis.

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ProNGF Expression and Targeting in Glioblastoma Multiforme

Cited by 5 publications

References 41 publications

The Crosstalk between Nerves and Cancer—A Poorly Understood Phenomenon and New Possibilities

The Crosstalk between Nerves and Cancer—A Poorly Understood Phenomenon and New Possibilities

The Membrane Protein Sortilin Is a Potential Biomarker and Target for Glioblastoma

NCDN is a Potential Biomarker and Therapeutic Target for Glioblastoma

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