keyword
https://read.qxmd.com/read/36012149/chaperone-mediated-autophagy-in-pericytes-a-key-target-for-the-development-of-new-treatments-against-glioblastoma-progression
#21
REVIEW
María Dolores Salinas, Rut Valdor
Glioblastoma (GB) cells physically interact with peritumoral pericytes (PCs) present in the brain microvasculature. These interactions facilitate tumor cells to aberrantly increase and benefit from chaperone-mediated autophagy (CMA) in the PC. GB-induced CMA leads to major changes in PC immunomodulatory phenotypes, which, in turn, support cancer progression. In this review, we focus on the consequences of the GB-induced up-regulation of CMA activity in PCs and evaluate how manipulation of this process could offer new strategies to fight glioblastoma, increasing the availability of treatments for this cancer that escapes conventional therapies...
August 10, 2022: International Journal of Molecular Sciences
https://read.qxmd.com/read/35871725/-latest-research-findings-on-the-role-of-non-tumor-cells-in-glioma-microenvironment
#22
REVIEW
Ming-Rong Zuo, Yan-Hui Liu
As the tumor cell-centered treatment strategies cannot curb the malignant progression of glioblastoma effectively, the therapeutic effect of glioblastoma is still not satisfactory. In addition to glioma cells, glioma microenvironment (GME) comprises massive numbers of non-tumor cells and soluble cytokines. The non-tumor cells include endothelial cells, pericytes, microglia/macrophages, mesenchymal cells, astrocytes, neurons, etc. These non-tumor cell components, together with glioma cells, form one organism which regulates the progression of glioma...
July 2022: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://read.qxmd.com/read/35869574/biomanufacturing-of-glioblastoma-organoids-exhibiting-hierarchical-and-spatially-organized-tumor-microenvironment-via-transdifferentiation
#23
JOURNAL ARTICLE
Seungjo Park, Alexandra D Avera, Yonghyun Kim
Glioblastoma (GBM) is the most aggressive type of brain tumor that originates from glioblastoma stem cells (GSCs). In the brain, GSCs are supported by a tumor microenvironment (TME) residing in the perivascular niche and the hypoxic niche. The GBM TME is highly heterogenous and exhibits complex cell-to-cell interactions. Three-dimensional tumorspheres cultured in stem cell-enriching media is often used as an in vitro model. The GBM tumorspheres retain some of the transcriptional and translational GSC features but often fails to recapitulate intertumor heterogeneity...
July 22, 2022: Biotechnology and Bioengineering
https://read.qxmd.com/read/35648828/a-predictive-microfluidic-model-of-human-glioblastoma-to-assess-trafficking-of-blood-brain-barrier-penetrant-nanoparticles
#24
JOURNAL ARTICLE
Joelle P Straehla, Cynthia Hajal, Hannah C Safford, Giovanni S Offeddu, Natalie Boehnke, Tamara G Dacoba, Jeffrey Wyckoff, Roger D Kamm, Paula T Hammond
Significance The blood-brain barrier represents a major therapeutic challenge for the treatment of glioblastoma, and there is an unmet need for in vitro models that recapitulate human biology and are predictive of in vivo response. Here, we present a microfluidic model of vascularized glioblastoma featuring a tumor spheroid in direct contact with self-assembled vascular networks comprising human endothelial cells, astrocytes, and pericytes. This model was designed to accelerate the development of targeted nanotherapeutics and enabled rigorous assessment of a panel of surface-functionalized nanoparticles designed to exploit a receptor overexpressed in tumor-associated vasculature...
June 7, 2022: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/35419364/chaperone-mediated-autophagy-ablation-in-pericytes-reveals-new-glioblastoma-prognostic-markers-and-efficient-treatment-against-tumor-progression
#25
JOURNAL ARTICLE
María Luisa Molina, David García-Bernal, María Dolores Salinas, Gonzalo Rubio, Pedro Aparicio, José M Moraleda, Salvador Martínez, Rut Valdor
Background: The lack of knowledge of the progression mechanisms of glioblastoma (GB), the most aggressive brain tumor, contributes to the absence of successful therapeutic strategies. Our team has recently demonstrated a crucial new role for chaperone-mediated autophagy (CMA) in pericytes (PC)-acquired immunosuppressive function, which prevents anti-tumor immune responses and facilitates GB progression. The possible impact that GB-induced CMA in PC has on other functions that might be useful for future GB prognosis/treatment, has not been explored yet...
2022: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/35141013/enhanced-proton-treatment-with-a-ldlr-ligand-peptide-conjugated-gold-nanoparticles-targeting-the-tumor-microenvironment-in-an-infiltrative-brain-tumor-model
#26
JOURNAL ARTICLE
Seungjun Seo, Eun Ho Kim, Won-Seok Chang, Won-Seok Lee, Ki-Hwan Kim, Jong-Ki Kim
The tumor microenvironment (TME) of glioblastoma malforms (GBMs) contains tumor invasiveness factors, microvascular proliferation, migratory cancer stem cells and infiltrative tumor cells, which leads to tumor recurrence in the absence of effective drug delivery in a Blood Brain Barrier (BBB)-intact TME and radiological invisibility. Low-density lipoprotein receptor (LDLR) is abundant in the blood brain barrier and overexpressed in malignant glioma cells. This study aimed to treat the TME with transmitted proton sensitization of LDLR ligand-functionalized gold nanoparticles (ApoB@AuNPs) in an infiltrative F98 glioma rat model...
2022: American Journal of Cancer Research
https://read.qxmd.com/read/35131870/chaperone-mediated-autophagy-controls-proteomic-and-transcriptomic-pathways-to-maintain-glioma-stem-cell-activity
#27
JOURNAL ARTICLE
Jaione Auzmendi-Iriarte, Maddalen Otaegi-Ugartemendia, Estefania Carrasco-Garcia, Mikel Azkargorta, Antonio Diaz, Ander Saenz-Antoñanzas, Joaquin Andrés Andermatten, Mikel Garcia-Puga, Idoia Garcia, Alejandro Elua-Pinin, Irune Ruiz, Nicolas Sampron, Felix Elortza, Ana Maria Cuervo, Ander Matheu
Chaperone-mediated autophagy (CMA) is a homeostatic process essential for the lysosomal degradation of a selected subset of the proteome. CMA activity directly depends on the levels of LAMP2A, a critical receptor for CMA substrate proteins at the lysosomal membrane. In glioblastoma (GBM), the most common and aggressive brain cancer in adulthood, high levels of LAMP2A in the tumor and tumor-associated pericytes have been linked to temozolomide resistance and tumor progression. However, the role of LAMP2A, and hence CMA, in any cancer stem cell type or in glioblastoma stem cells (GSC) remains unknown...
April 1, 2022: Cancer Research
https://read.qxmd.com/read/35057010/neuroimmunomodulatory-properties-of-flavonoids-and-derivates-a-potential-action-as-adjuvants-for-the-treatment-of-glioblastoma
#28
REVIEW
Ravena Pereira do Nascimento, Balbino Lino Dos Santos, Jéssika Alves Oliveira Amparo, Janaina Ribeiro Pereira Soares, Karina Costa da Silva, Monique Reis Santana, Áurea Maria Alves Nunes Almeida, Victor Diógenes Amaral da Silva, Maria de Fátima Dias Costa, Henning Ulrich, Vivaldo Moura-Neto, Giselle Pinto de Faria Lopes, Silvia Lima Costa
Glioblastomas (GBMs) are tumors that have a high ability to migrate, invade and proliferate in the healthy tissue, what greatly impairs their treatment. These characteristics are associated with the complex microenvironment, formed by the perivascular niche, which is also composed of several stromal cells including astrocytes, microglia, fibroblasts, pericytes and endothelial cells, supporting tumor progression. Further microglia and macrophages associated with GBMs infiltrate the tumor. These innate immune cells are meant to participate in tumor surveillance and eradication, but they become compromised by GBM cells and exploited in the process...
January 4, 2022: Pharmaceutics
https://read.qxmd.com/read/34685606/disproportion-in-pericyte-endothelial-cell-proliferation-and-mechanisms-of-intussusceptive-angiogenesis-participate-in-bizarre-vessel-formation-in-glioblastoma
#29
JOURNAL ARTICLE
Lucio Díaz-Flores, Ricardo Gutiérrez, Miriam González-Gómez, María-Del-Pino García, Lucio Díaz-Flores, Ibrahim González-Marrero, Julio Ávila, Pablo Martín-Vasallo
Glioblastoma (GBM) is the most malignant tumor in the brain. In addition to the vascular pattern with thin-walled vessels and findings of sprouting angiogenesis, GBM presents a bizarre microvasculature (BM) formed by vascular clusters, vascular garlands, and glomeruloid bodies. The mechanisms in BM morphogenesis are not well known. Our objective was to assess the role of pericyte/endothelial proliferation and intussusceptive angiogenic mechanisms in the formation of the BM. For this purpose, we studied specimens of 66 GBM cases using immunochemistry and confocal microscopy...
October 1, 2021: Cells
https://read.qxmd.com/read/34535655/pericyte-derived-fibrotic-scarring-is-conserved-across-diverse-central-nervous-system-lesions
#30
JOURNAL ARTICLE
David O Dias, Jannis Kalkitsas, Yildiz Kelahmetoglu, Cynthia P Estrada, Jemal Tatarishvili, Daniel Holl, Linda Jansson, Shervin Banitalebi, Mahmood Amiry-Moghaddam, Aurélie Ernst, Hagen B Huttner, Zaal Kokaia, Olle Lindvall, Lou Brundin, Jonas Frisén, Christian Göritz
Fibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic tissue generation and distribution of stromal cells across different lesions in the brain and spinal cord has not been systematically investigated in mice and humans. Furthermore, it is unknown whether scar-forming stromal cells have the same origin throughout the central nervous system and in different types of lesions. In the current study, we compared fibrotic scarring in human pathological tissue and corresponding mouse models of penetrating and non-penetrating spinal cord injury, traumatic brain injury, ischemic stroke, multiple sclerosis and glioblastoma...
September 17, 2021: Nature Communications
https://read.qxmd.com/read/34474820/multifunctional-silica-coated-mixed-polymeric-micelles-for-integrin-targeted-therapy-of-pediatric-patient-derived-glioblastoma
#31
JOURNAL ARTICLE
Prakram Singh Chauhan, Murali Kumarasamy, Angel M Carcaboso, Alejandro Sosnik, Dganit Danino
Glioblastoma multiforme (GBM) remains a major cause of mortality because treatments are precluded by to the limited transport and penetration of chemotherapeutics across the blood-brain barrier. Pitavastatin (PTV) is a hydrophobic Food and Drug Administration (FDA)-approved anticholesterolemic agent with reported anti-GBM activity. In the present study, we encapsulate PTV in silica-coated polymeric micelles (SiO2 PMs) surface-modified with the cyclic peptide Arg-Gly-Asp-Phe-Val (cRGDfV) that actively targets the αv β3 integrin overexpressed in the BBB endothelium and GBM...
September 2021: Materials Science & Engineering. C, Materials for Biological Applications
https://read.qxmd.com/read/34407932/microengineered-perfusable-3d-bioprinted-glioblastoma-model-for-in-vivo-mimicry-of-tumor-microenvironment
#32
JOURNAL ARTICLE
Lena Neufeld, Eilam Yeini, Noa Reisman, Yael Shtilerman, Dikla Ben-Shushan, Sabina Pozzi, Asaf Madi, Galia Tiram, Anat Eldar-Boock, Shiran Ferber, Rachel Grossman, Zvi Ram, Ronit Satchi-Fainaro
Many drugs show promising results in laboratory research but eventually fail clinical trials. We hypothesize that one main reason for this translational gap is that current cancer models are inadequate. Most models lack the tumor-stroma interactions, which are essential for proper representation of cancer complexed biology. Therefore, we recapitulated the tumor heterogenic microenvironment by creating fibrin glioblastoma bioink consisting of patient-derived glioblastoma cells, astrocytes, and microglia. In addition, perfusable blood vessels were created using a sacrificial bioink coated with brain pericytes and endothelial cells...
August 2021: Science Advances
https://read.qxmd.com/read/34361013/netrin-1-in-glioblastoma-neovascularization-the-new-partner-in-crime
#33
REVIEW
Ximena Vásquez, Pilar Sánchez-Gómez, Verónica Palma
Glioblastoma (GBM) is the most aggressive and common primary tumor of the central nervous system. It is characterized by having an infiltrating growth and by the presence of an excessive and aberrant vasculature. Some of the mechanisms that promote this neovascularization are angiogenesis and the transdifferentiation of tumor cells into endothelial cells or pericytes. In all these processes, the release of extracellular microvesicles by tumor cells plays an important role. Tumor cell-derived extracellular microvesicles contain pro-angiogenic molecules such as VEGF, which promote the formation of blood vessels and the recruitment of pericytes that reinforce these structures...
July 31, 2021: International Journal of Molecular Sciences
https://read.qxmd.com/read/34359800/apln-aplnr-signaling-controls-key-pathological-parameters-of-glioblastoma
#34
REVIEW
Roland E Kälin, Rainer Glass
Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. GBM-expansion depends on a dense vascular network and, coherently, GBMs are highly angiogenic. However, new intratumoral blood vessels are often aberrant with consequences for blood-flow and vascular barrier function. Hence, the delivery of chemotherapeutics into GBM can be compromised. Furthermore, leaky vessels support edema-formation, which can result in severe neurological deficits. The secreted signaling peptide Apelin (APLN) plays an important role in the formation of GBM blood vessels...
August 2, 2021: Cancers
https://read.qxmd.com/read/34286445/ccl27-signaling-in-the-tumor-microenvironment
#35
REVIEW
Miguel Martínez-Rodríguez, Carlos Monteagudo
Chemokines are a group of small proteins which play an important role in leukocyte migration and invasion. They are also involved in the cellular proliferation and migration of tumor cells.Chemokine CCL27 (cutaneous T cell-attracting chemokine, CTACK) is mainly expressed by keratinocytes of the normal epidermis. It is well known that this chemokine plays an important role in several inflammatory diseases of the skin, such as atopic dermatitis, contact dermatitis, and psoriasis. Moreover, several studies have shown an association between CCL27 expression and a variety of neoplasms including skin cancer...
2021: Advances in Experimental Medicine and Biology
https://read.qxmd.com/read/34282761/fibroblast-activation-protein-expressing-mesenchymal-cells-promote-glioblastoma-angiogenesis
#36
JOURNAL ARTICLE
Eva Balaziova, Petr Vymola, Petr Hrabal, Rosana Mateu, Michal Zubal, Robert Tomas, David Netuka, Filip Kramar, Zuzana Zemanova, Karla Svobodova, Marek Brabec, Aleksi Sedo, Petr Busek
Fibroblast activation protein (FAP) is a membrane-bound protease that is upregulated in a wide range of tumours and viewed as a marker of tumour-promoting stroma. Previously, we demonstrated increased FAP expression in glioblastomas and described its localisation in cancer and stromal cells. In this study, we show that FAP+ stromal cells are mostly localised in the vicinity of activated CD105+ endothelial cells and their quantity positively correlates with glioblastoma vascularisation. FAP+ mesenchymal cells derived from human glioblastomas are non-tumorigenic and mostly lack the cytogenetic aberrations characteristic of glioblastomas...
July 1, 2021: Cancers
https://read.qxmd.com/read/34267351/neutralizing-shapeshifting-pericytes-enhances-glioblastoma-therapeutic-efficacy
#37
COMMENT
Samuel A Sprowls, Justin D Lathia
No abstract text is available yet for this article.
October 2021: Cell Research
https://read.qxmd.com/read/34239070/pericytes-augment-glioblastoma-cell-resistance-to-temozolomide-through-ccl5-ccr5-paracrine-signaling
#38
JOURNAL ARTICLE
Xiao-Ning Zhang, Kai-Di Yang, Cong Chen, Zhi-Cheng He, Qiang-Hu Wang, Hua Feng, Sheng-Qing Lv, Yan Wang, Min Mao, Qing Liu, Yao-Yao Tan, Wen-Ying Wang, Tian-Ran Li, Lin-Rong Che, Zhong-Yi Qin, Ling-Xiang Wu, Min Luo, Chun-Hua Luo, Yu-Qi Liu, Wen Yin, Chao Wang, Hai-Tao Guo, Qing-Rui Li, Bin Wang, Wei Chen, Shuang Wang, Yu Shi, Xiu-Wu Bian, Yi-Fang Ping
Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis...
October 2021: Cell Research
https://read.qxmd.com/read/34070840/cald1-modulates-gliomas-progression-via-facilitating-tumor-angiogenesis
#39
JOURNAL ARTICLE
Quan Cheng, Anliu Tang, Zeyu Wang, Ning Fang, Zhuojing Zhang, Liyang Zhang, Chuntao Li, Yu Zeng
Angiogenesis is more prominent in anaplastic gliomas and glioblastoma (GBM) than that in pilocytic and diffuse gliomas. Caldesmon (CALD1) plays roles in cell adhesion, cytoskeletal organization, and vascularization. However, limited information is available on mechanisms underlying the effect of CALD1 on the microvascular facilitation and architecture in glioma. In this study, we explored the role of CALD1 in gliomas by integrating bulk RNA-seq analysis and single cell RNA-seq analysis. A positive correlation between CALD1 expression and the gliomas' pathological grade was noticed, according to the samples from the TCGA and CGGA database...
May 30, 2021: Cancers
https://read.qxmd.com/read/34018679/upregulated-functional-gene-expression-programmes-in-tumour-pericytes-mark-progression-in-patients-with-low-grade-glioma
#40
JOURNAL ARTICLE
Clara Oudenaarden, Jonas Sjölund, Kristian Pietras
Pericytes conceivably play important roles in the tumour microenvironment of glioblastoma multiforme (GBM) by allowing for an aberrant vasculature and acting as a component in the perivascular niche that supports glioma stem-like cells. However, a lack of specific markers has hampered in-depth elucidation of the functional contribution of pericytes to GBM. This study provides a comprehensive computational biology approach to annotate pericyte marker genes in the GBM vasculature through integration of data from single-cell RNA-sequencing studies of both mouse and human tissue, as well as bulk tumour- and healthy-tissue gene expression data from patients with GBM...
May 21, 2021: Molecular Oncology
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