Glioblastoma Microenvironment and Invasiveness: New Insights and Therapeutic Targets

Author:

Erices José Ignacio12ORCID,Bizama Carolina34ORCID,Niechi Ignacio12ORCID,Uribe Daniel1,Rosales Arnaldo12,Fabres Karen1,Navarro-Martínez Giovanna12,Torres Ángelo5,San Martín Rody6,Roa Juan Carlos34ORCID,Quezada-Monrás Claudia12

Affiliation:

1. Laboratorio de Biología Tumoral, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Valdivia 5090000, Chile

2. Millennium Institute on Immunology and Immunotherapy, Universidad Austral de Chile, Valdivia 5090000, Chile

3. Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile

4. Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile

5. Escuela de Medicina Veterinaria, Facultad de Recursos Naturales y Medicina Veterinaria, Universidad Santo Tomás, Talca 8370003, Chile

6. Laboratorio de Patología Molecular, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Valdivia 5090000, Chile

Abstract

Glioblastoma (GBM) is the most common and malignant primary brain cancer in adults. Without treatment the mean patient survival is approximately 6 months, which can be extended to 15 months with the use of multimodal therapies. The low effectiveness of GBM therapies is mainly due to the tumor infiltration into the healthy brain tissue, which depends on GBM cells’ interaction with the tumor microenvironment (TME). The interaction of GBM cells with the TME involves cellular components such as stem-like cells, glia, endothelial cells, and non-cellular components such as the extracellular matrix, enhanced hypoxia, and soluble factors such as adenosine, which promote GBM’s invasiveness. However, here we highlight the role of 3D patient-derived glioblastoma organoids cultures as a new platform for study of the modeling of TME and invasiveness. In this review, the mechanisms involved in GBM-microenvironment interaction are described and discussed, proposing potential prognosis biomarkers and new therapeutic targets.

Funder

Fondecyt regular

(RSM) Agencia Nacional de Investigación y Desarrollo (ANID)—Millennium Science Initiative Program

Millennium Institute on Immunology and Immunotherapy

(CQ-M)

Vicerrectoría de Investigación, Desarrollo y Creación artistica VIDCA-UACh

CONICYT Postgraduate scholarship

Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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