Expression of SCD and FADS2 Is Lower in the Necrotic Core and Growing Tumor Area than in the Peritumoral Area of Glioblastoma Multiforme

Abstract

The expression of desaturases is higher in many types of cancer, and despite their recognized role in oncogenesis, there has been no research on the expression of desaturases in glioblastoma multiforme (GBM). Tumor tissue samples were collected during surgery from 28 patients (16 men and 12 women) diagnosed with GBM. The effect of necrotic conditions and nutritional deficiency (mimicking conditions in the studied tumor zones) was studied in an in vitro culture of human brain (glioblastoma astrocytoma) U-87 MG cells. Analysis of desaturase expression was made by qRT-PCR and the immunohistochemistry method. In the tumor, the expression of stearoyl–coenzyme A desaturase (SCD) and fatty acid desaturases 2 (FADS2) was lower than in the peritumoral area. The expression of other desaturases did not differ in between the distinguished zones. We found no differences in the expression of SCD, fatty acid desaturases 1 (FADS1), or FADS2 between the sexes. Necrotic conditions and nutritional deficiency increased the expression of the studied desaturase in human brain (glioblastoma astrocytoma) U-87 MG cells. The obtained results suggest that (i) biosynthesis of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) in a GBM tumor is less intense than in the peritumoral area; (ii) expressions of SCD, SCD5, FADS1, and FADS2 correlate with each other in the necrotic core, growing tumor area, and peritumoral area; (iii) expressions of desaturases in a GBM tumor do not differ between the sexes; and (iv) nutritional deficiency increases the biosynthesis of MUFA and PUFA in GBM cells.

GBM tumors are heterogeneous in their fatty acid metabolism and modulating fatty acid metabolism sensitizes cancer cells derived from recurring GBM tumors to temozolomide

“…This is in line with previous findings showing that FASN expression is correlated with stemness (39) and its inhibition induces apoptosis in patient derived GBM cells (40). It was also shown that CD133 + glioma stem cells from in vitro cultured neurospheres display elevated FADS1 and FADS2 activities (41) and that SCD and FADS2 exhibit spatial heterogeneity with higher expression in the peritumoral area (42).…”

Glioblastoma Multiforme Tumors in Women Have a Lower Expression of Fatty Acid Elongases ELOVL2, ELOVL5, ELOVL6, and ELOVL7 than in Men

“…To produce nutrient deficiency, U-87 MG cells were incubated with a low concentration of L-glutamine (0.2 mM) and without sodium pyruvate (volume supplemented with PBS), leaving 1.0 g/L (5.5 mM) of glucose in the medium. These conditions have been described by us and applied in a previous work in which we studied the expression of fatty acid desaturases in GBM [ 19 ]. After 24 h of incubation under those conditions, the U-87 MG cells were trypsinized, and the resulting cell pellet was washed with PBS solution and centrifuged again (25 °C, 300 G, 5 min).…”

“…In a previous study, we analyzed changes in the expression of fatty acid desaturases in GBM and found a reduction in the expression of SCD and FADS2 in GBM tumors, with no differences in the expression of fatty acid desaturases between women and men [ 19 ]. In order to have a thorough understanding of the fatty acid synthesis pathways in GBM, it is necessary to study the expression of elongases, especially in relation to the gender of the GBM tumor patients—men have a worse prognosis and lower survival rate than women [ 20 , 21 ].…”

Construction of a Risk Model to Predict the Prognosis and Immunotherapy of Low-Grade Glioma Ground on 7 Ferroptosis-Related Genes

“… 40 Stearoyl-CoA desaturase (SCD) is abnormally expressed in glioblastoma multiforme and is associated with patient prognosis. 41 SCD is overexpressed in glioma cells and can regulate lipid metabolism and organelle morphology, which has unique therapeutic significance. 42 Solute carrier family 1 member 5 (SLC1A5) is abnormally expressed in glioma, and the overexpression of SLC1A5 can eliminate the inhibitory effect of lncRNA-XIST down-regulation on glioma activity and tumorigenesis.…”