Page 18 - Read Online

Topic: Brain tumor cell invasion and metastasis: anatomical, biological and clinical considerations

Effects of Gas1 on gliomas: a review on current preclinical studies

Jose Segovia, Elizabeth Bautista, Manuel Lara-Lozano
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, 07360 Distrito Federal, Mexico.
Correspondence to: Dr. Jose Segovia, Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del
IPN, 07360 Distrito Federal, Mexico. E-mail: jsegovia@fisio.cinvestav.mx

A B S T R AC T
Glioblastoma multiforme (GBM) is the most common and lethal brain tumor. Its prognosis remains very poor, despite the use of combined
treatments such as surgical resection, radiation and chemotherapy. The major limitations for the treatment of GBM are its high invasiveness,
tumor recurrence and resistance to treatments. Therefore, gene therapy appears as a relevant strategy for its treatment. Thus, we have
investigated the use of growth-arrest-specific 1 (Gas1) for the treatment of GBM. Gas1 is a tumor suppressor protein that inhibits glioma
growth by inducing arrest and apoptosis of tumor cells. Moreover, we have shown that a soluble form of Gas1 acting in both autocrine and
paracrine manners is also effective inhibiting tumor growth in animal models, indicating its potential as an adjuvant for the treatment of
GBM.
Key words: Growth arrest specific 1; glioma; serine-threonine protein kinase; glial cell-derived neurotrophic factor;
extracellular signal-regulated kinases and tumor

INTRODUCTION Tumors of glial origin are considered gliomas and are divided
into: astrocytoma, oligodendroglioma, ependymoma,
Gliomas are the most frequent and aggressive tumors of mixed gliomas and not otherwise specified. [2,3] On the other
the central nervous system (CNS) and current treatments hand, The Cancer Genome Atlas (TCGA) designed a sub-
have not improved their prognosis. In children and classification of GBM based on their molecular signature
adolescents, tumors of the CNS are the most common and [Table 1], which comprises: classical, mesenchymal,
lethal; and glioblastoma multiforme (GBM) is the most proneural and neural tumors. [8,9] Classical GBM are tumors
[1]
frequent malignant primary brain tumor. [2-5] Gliomas are that present high expression of the epidermal growth
the main neuroepithelial tumors of the CNS that originate factor receptor (EGFR) and absence of tumor suppressor
from mature or precursor ectodermal-derived glial cells. proteins such as p16 and p14. In mesenchymal GBM,
The World Health Organization (WHO) has classified the phosphatase and tensin homolog (PTEN) gene is
mutated and loss of its activity leads to activation of the
gliomas on 4 grades from I to IV (GI-GIV) according to the serine-threonine protein kinase (AKT) survival pathway.
histological dedifferentiation and the expression of the KI- Additionally, this subtype expresses chitinase 3-like-1
67 protein, which indicates the rate of proliferation. WHO- and MET transcripts characteristics of mesenchymal cells
GI gliomas are considered as benign tumors, since the and shows low expression of the transcript for the tumor
malignant features are only present on low-grade (WHO- suppressor protein neurofibromin 1. On the other hand,
GII) and high-grade (WHO-GIII and -GIV) gliomas; in this proneural GBM expresses oligodendrocyte transcripts
respect, WHO classification correlates with the prognosis NK2 homeobox 2 and oligodendrocyte transcription factor
of the patient, regardless of multimodal therapeutic (OLIG2), as well as high levels of platelet-derived growth
treatments; [6,7] the 5-year life span rates after diagnosis are factor (PDGF) receptor, alpha polypeptide, and mutations
50%, 30% and 5% for WHO-GII, -GIII and -GIV glioma of the dehydrogenase 1 and/or P53 genes. The neural GBM
patients, respectively. [8] is the most dedifferentiated subtype because it expresses

This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
Access this article online others to remix, tweak, and build upon the work non-commercially, as long as
the author is credited and the new creations are licensed under the identical
Quick Response Code: terms.
Website:
www.jcmtjournal.com For reprints contact: service@oaepublish.com
How to cite this article: Segovia J, Bautista E, Lara-Lozano M.
Effects of Gas1 on gliomas: a review on current preclinical studies. J
DOI: Cancer Metastasis Treat 2016;2:101-11.
10.20517/2394-4722.2015.76
Received: 14-10-2015; Accepted: 30-11-2015.

©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc. 101