VEGFC negatively regulates the growth and aggressiveness of medulloblastoma cells

Penco-Campillo, Manon; Comoglio, Yannick; Morel, Álvaro Javier Feliz; Hanna, Rita; Durivault, Jérôme; Leloire, Magalie; Mejias, Bastien; Pagnuzzi, Marina; Morot, Amandine; Burel‐Vandenbos, Fanny; Selby, Matthew; Williamson, Daniel; Clifford, Steven C.; Claren, Audrey; Doyen, J.; Picco, Vincent; Martial, Sonia; Pagès, Gilles

doi:10.1038/s42003-020-01306-4

Cited by 11 publications

(10 citation statements)

References 62 publications

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“…The concept of vasculogenic mimicry corresponds to vessel-like formation by endothelial cells or some tumour cells that exhibit invasive capacity [ 53 , 54 ]. Daoy, ONS-76, and HD-MB03 cells were able to organize as pseudo-vessels [ 55 ], and D341Med cells were unable to do so.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, any treatment that can induce the death of tumour cells that have survived multiple cycles of radiation is an important breakthrough. To test the relevance of C29 after relapse, we generated radiation-resistant Daoy and HD-MB03 cells to simulate relapse after radiotherapy [ 55 ]. Two independent populations were generated for each cell line.…”

Section: Resultsmentioning

confidence: 99%

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Targeting of the ELR+CXCL/CXCR1/2 Pathway Is a Relevant Strategy for the Treatment of Paediatric Medulloblastomas

Penco-Campillo

Molina

Piris

et al. 2022

Cells

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Medulloblastoma (MB) is the most common and aggressive paediatric brain tumour. Although the cure rate can be as high as 70%, current treatments (surgery, radio- and chemotherapy) excessively affect the patients’ quality of life. Relapses cannot be controlled by conventional or targeted treatments and are usually fatal. The strong heterogeneity of the disease (four subgroups and several subtypes) is related to innate or acquired resistance to reference treatments. Therefore, more efficient and less-toxic therapies are needed. Here, we demonstrated the efficacy of a novel inhibitor (C29) of CXCR1/2 receptors for ELR+CXCL cytokines for the treatment of childhood MB. The correlation between ELR+CXCL/CXCR1/2 expression and patient survival was determined using the R2: Genomics Analysis and Visualization platform. In vitro efficacy of C29 was evaluated by its ability to inhibit proliferation, migration, invasion, and pseudo-vessel formation of MB cell lines sensitive or resistant to radiotherapy. The growth of experimental MB obtained by MB spheroids on organotypic mouse cerebellar slices was also assayed. ELR+CXCL/CXCR1/2 levels correlated with shorter survival. C29 inhibited proliferation, clone formation, CXCL8/CXCR1/2-dependent migration, invasion, and pseudo-vessel formation by sensitive and radioresistant MB cells. C29 reduced experimental growth of MB in the ex vivo organotypic mouse model and crossed the blood–brain barrier. Targeting CXCR1/2 represents a promising therapeutic strategy for the treatment of paediatric MB in first-line treatment or after relapse following conventional therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Targeting of the ELR+CXCL/CXCR1/2 Pathway Is a Relevant Strategy for the Treatment of Paediatric Medulloblastomas

Penco-Campillo

Molina

Piris

et al. 2022

Cells

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“…Previous studies found that VEGF‐C system plays neurotrophic roles in neural development [ 11 , 12 , 32 ] and neurological diseases, such as ischemia [ 13 , 33 , 34 , 35 ], brain tumor [ 36 , 37 , 38 ], and Alzheimer's disease [ 39 ]. In patients with epilepsy and animal models, VEGF‐C and its receptors were found to be upregulated in the epileptogenic foci [ 15 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Vascular endothelial growth factor‐C modulates cortical NMDA receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia

Shen

Duan

et al. 2022

Brain Pathology

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Emergence of dysmorphic neurons is the primary pathology in focal cortical dysplasia (FCD) associated pediatric intractable epilepsy; however, the etiologies related to the development and function of dysmorphic neurons are not fully understood. Our previous studies revealed that the expression of vascular endothelial growth factor‐C (VEGF‐C) and corresponding receptors VEGFR‐2, VEGFR‐3 was increased in the epileptic lesions of patients with tuberous sclerosis complex or mesial temporal lobe epilepsy. Here, we showed that the expression of VEGF‐C, VEGFR‐2, and VEGFR‐3 was increased at both mRNA and protein levels in patients with cortical lesions of type I, IIa, and IIb FCD. The immunoreactivity of VEGF‐C, VEGFR‐2 and VEGFR‐3 was located in the micro‐columnar neurons in FCD type I lesions, dysplastic neurons (DNs) in FCD type IIa lesions, balloon cells (BCs) and astrocytes in FCD type IIb lesions. Additionally, the amplitude of evoked‐EPSCs (eEPSC) mediated by NMDA receptor, the ratio of NMDA receptor‐ and AMPA receptor‐mediated eEPSC were increased in the dysmorphic neurons of FCD rats established by prenatal X‐ray radiation. Furthermore, NMDA receptor mediated current in dysmorphic neurons was further potentiated by exogenous administration of VEGF‐C, however, could be antagonized by ki8751, the blocker of VEGFR‐2. These results suggest that VEGF‐C system participate in the pathogenesis of cortical lesions in patients with FCD in association with modulating NMDA receptor–mediated currents.

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“…However, tumor cells also use lymphatic vessels to migrate and metastasize, which has implications for treatments. Interestingly, the main lymphatic endothelial cell growth factor VEGFC, which promotes the sprouting of lymphatic vessels, has been associated with anti-tumoral effects in MB [ 164 ]. This indicates that the lymphatic system might be beneficial in preventing MB growth as opposed to the current understanding in other cancers.…”

Section: Targeting the Brain Tumor Vasculature In Medulloblastomamentioning

confidence: 99%

The Tumor Microenvironment of Medulloblastoma: An Intricate Multicellular Network with Therapeutic Potential

Bree

Wilhelm

2022

Cancers

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Medulloblastoma (MB) is a heterogeneous disease in which survival is highly affected by the underlying subgroup-specific characteristics. Although the current treatment modalities have increased the overall survival rates of MB up to 70–80%, MB remains a major cause of cancer-related mortality among children. This indicates that novel therapeutic approaches against MB are needed. New promising treatment options comprise the targeting of cells and components of the tumor microenvironment (TME). The TME of MB consists of an intricate multicellular network of tumor cells, progenitor cells, astrocytes, neurons, supporting stromal cells, microglia, immune cells, extracellular matrix components, and vasculature systems. In this review, we will discuss all the different components of the MB TME and their role in MB initiation, progression, metastasis, and relapse. Additionally, we briefly introduce the effect that age plays on the TME of brain malignancies and discuss the MB subgroup-specific differences in TME components and how all of these variations could affect the progression of MB. Finally, we highlight the TME-directed treatments, in which we will focus on therapies that are being evaluated in clinical trials.

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VEGFC negatively regulates the growth and aggressiveness of medulloblastoma cells

Cited by 11 publications

References 62 publications

Targeting of the ELR+CXCL/CXCR1/2 Pathway Is a Relevant Strategy for the Treatment of Paediatric Medulloblastomas

Targeting of the ELR+CXCL/CXCR1/2 Pathway Is a Relevant Strategy for the Treatment of Paediatric Medulloblastomas

Vascular endothelial growth factor‐C modulates cortical NMDA receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia

The Tumor Microenvironment of Medulloblastoma: An Intricate Multicellular Network with Therapeutic Potential

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