Oncotarget | Glypican-1 in human glioblastoma: implications in tumorigenesis and chemotherapy

Oncotarget Volume 11, Issue 9 reported that this study aimed to investigate how glypican-1 influences the tumoral profile of human glioblastoma using in vitro cell line models.

Therefore, we present evidence not only to support facts that glypican-1 is an elementary macromolecule in glioblastoma tumoral microenvironment but also to introduce this proteoglycan as a promising therapeutic target for this lethal tumor.

Dr. Leny Toma from the Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, SP, Brazil said, "The most frequent central nervous system (CNS) malignant tumors are the gliomas, which arise from glial precursor cells, and can be divided into oligodendrogliomas, oligoastrocytomas, ependymomas, astrocytomas, and some minor classifications."

"The most frequent central nervous system (CNS) malignant tumors are the gliomas, which arise from glial precursor cells, and can be divided into oligodendrogliomas, oligoastrocytomas, ependymomas, astrocytomas, and some minor classifications."

- Dr. Leny Toma, the Department of Biochemistry, Universidade Federal de São Paulo

Other GAGs are chondroitin sulfate, dermatan sulfate, keratan sulfate, hyaluronic acid, and heparin.

Heparan sulfate proteoglycans are known to participate in various aspects of cell signaling.

The syndecans, with four isoforms, and glypicans, with six isoforms, are membrane-bound and generally located in lipid rafts; they can interact with morphogens such as ligands from the Wnt, Hh, and FGF families in a manner to facilitate interaction with their receptors.

Figure 1: GPC1 knock-down clone selection. Dose-dependent response of TS543 neurospheres to CBD (0-40 μM). (A) All generated monoclonal cell lines had the GPC1 expression quantified by RT-qPCR. Dotted lines represent 50% and 80% of GPC1 silencing, respectively and, when more than 80% of gene silencing was achieved, the percentage reduction is indicated. (B) Flow cytometry assessment of GPC1 in control GBM cells and the five most GPC1-silenced clones. This representation shows the fraction of GPC1⁺ cells for each group. (C) Representative histograms of GPC1 fluorescence intensity distribution. Unstained samples are represented by unfilled curves (controls, CN). (D) Transcriptional profile of membrane-bound HSPG, selected Wnt ligands, and MMPs that were assessed by RT-qPCR. The heatmap of 2^-ΔΔCt was generated, in which significant comparisons are not indicated but are commented on in the text. Gradients of red indicate diminished expression, and of green heightened expression in relation to U-251 MG. All data are plotted as mean ± SEM. The one-way ANOVA with the Dunnett's post-hoc test was performed, and statistically significant comparisons are marked as follows: ^*p < 0.05, ^**p < 0.01, ^***p 0.001 and ^****p < 0.0001 vs. U-251 MG. The sample size was n = 6 for RT-qPCR and n = 5 for flow cytometry.

Although GPC1 has received little focus in regard to glioblastoma, Saito & colleagues demonstrated how this molecule influences the lower survival of GBM patients.

Additionally, it has been previously shown that GPC1 may affect FGF-2 signaling in this tumor, contributing to its proliferative aspect and aggressiveness.

To that end, we would deplete GBM cells of the molecule and investigate biological, biochemical, and pharmacological aspects of the modified cell lines to obtain further answers of how this HSPG could influence the tumorigenic process of GBM.

The Toma Research Team concluded in their Oncotarget Research Paper that this study aimed to investigate whether GPC1 could modulate GBM tumoral behavior.

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Full text - https://doi.org/10.18632/oncotarget.27492

Correspondence to - Leny Toma - ltoma.bioq@gmail.com

Keywords - glioblastoma, glypican-1, tumorigenesis, chemotherapy resistance, temozolomide

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