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Cellular Conversations in Glioblastoma Progression, Diagnosis and Treatment

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Abstract

Glioblastoma (GBM) is the most frequent malignancy among primary brain tumors in adults and one of the worst 5-year survival rates (< 7%) among all human cancers. Till now, treatments that target particular cell or intracellular metabolism have not improved patients’ survival. GBM recruits healthy brain cells and subverts their processes to create a microenvironment that contributes to supporting tumor progression. This microenvironment encompasses a complex network in which malignant cells interact with each other and with normal and immune cells to promote tumor proliferation, angiogenesis, metastasis, immune suppression, and treatment resistance. Communication can be direct via cell-to-cell contact, mainly through adhesion molecules, tunneling nanotubes, gap junctions, or indirect by conventional paracrine signaling by cytokine, neurotransmitter, and extracellular vesicles. Understanding these communication routes could open up new avenues for the treatment of this lethal tumor. Hence, therapeutic approaches based on glioma cells` communication have recently drawn attention. This review summarizes recent findings on the crosstalk between glioblastoma cells and their tumor microenvironment, and the impact of this conversation on glioblastoma progression. We also discuss the mechanism of communication of glioma cells and their importance as therapeutic targets and diagnostic and prognostic biomarkers. Overall, understanding the biological mechanism of specific interactions in the tumor microenvironment may help in predicting patient prognosis and developing novel therapeutic strategies to target GBM.

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Data availability

Enquiries about data availability should be directed to the authors.

Abbreviations

ALDH:

Aldehyde dehydrogenase

BBB:

Blood–brain barrier

CAF:

Cancer-associated fibroblast

CM:

Conditioned media

CX:

Connexin

CXCL:

C-X-C motif chemokine ligand

CXCR:

C-X-C motif chemokine receptors

ECM:

Extracellular matrix

EVs:

Extracellular vesicles

FAPα:

Fibroblast activation protein alpha

FN:

Fibronectin

IBP-2:

Insulin-like growth factor-binging protein 2

IDH1:

Isocitrate dehydrogenase 1

JAK2:

Janus kinase 2

JNK:

C-Jun N-terminal kinase

GBM:

Glioblastoma

GSCs:

GBM stem-like cells

MYDGF:

Myeloid-derived growth factor

NK:

Natural killer

NLGN3:

Neuron-derived neuroligin-3

PD-L1:

Programmed death-ligand

RAS:

Rat sarcoma virus

SDF-1:

Stromal cell-derived factor-1

SOX2:

SRY (sex determining region Y)-box 2

STAT3:

Signal Transducer and Activator of Transcription 3

TEXs:

Tumor-derived exosome’s

TME:

Tumor microenvironment

TIMP-2:

Tissue inhibitor of metalloproteinases-2

TMs:

Tumor microtubes

TMZ:

Temozolomide

TNTs:

Tunneling nanotubes

WNT:

Wingless-related integration site

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Authors and Affiliations

  1. Brain Cancer Research Core (BCRC), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Ali Karimi Sisakht, Mohammad Malekan, Farbod Ghobadinezhad, Seyedeh Negar Mousavi Firouzabadi & Banafshe Abadi

  2. Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

    Ali Karimi Sisakht

  3. Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Mohammad Malekan

  4. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Mohammad Malekan

  5. Student Research Committee, Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Farbod Ghobadinezhad

  6. USERN Office, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Farbod Ghobadinezhad

  7. Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

    Seyedeh Negar Mousavi Firouzabadi

  8. Advanced Therapy Medicinal Product (ATMP) Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran

    Ameneh Jafari

  9. Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Ameneh Jafari

  10. School of Medicine, Kashan University of Medical Sciences, Kashan, Iran

    Seyed Mohammad Ali Mirazimi

  11. Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran

    Seyed Mohammad Ali Mirazimi

  12. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Banafshe Abadi

  13. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran

    Rana Shafabakhsh & Hamed Mirzaei

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  1. Ali Karimi Sisakht
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Sisakht, A.K., Malekan, M., Ghobadinezhad, F. et al. Cellular Conversations in Glioblastoma Progression, Diagnosis and Treatment. Cell Mol Neurobiol 43, 585–603 (2023). https://doi.org/10.1007/s10571-022-01212-9

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