Increased expression of a glutamine transporter SNAT3 is a marker of malignant gliomas

Abstract

Glutamine (Gln) is a growth determinant in neoplastic tissues. We analysed by RT-PCR the expression of mRNAs coding for the human variants of Gln transporters: ASCT2 (system ASC), SNAT1 [ATA1] (system A), SNAT3 [SN1] and SNAT5 [SN2] (system N), in samples of human malignant gliomas WHO grades III/IV (anaplastic astrocytoma and glioblastoma), glioma-derived cell cultures, brain metastases from peripheral organs, and control brain tissue. SNAT3 mRNA showed a 3-5 times stronger expression in gliomas than in metastases or control tissue, and was virtually absent from glioma cultures. Native glioblastoma immunostained positively with anti-SNAT3 antibody. The expression of ASCT2 mRNA, but not SNAT5 or SNAT1 mRNAs, was increased in all neoplastic tissues studied. Hence, increased expression of SNAT3 is a marker of primary malignant gliomas in situ.

The expression of the aminoacid transporters ASCT2 (SLC1A5) and LAT1 (SLC7A5) in astrocytomas

“…In the present study, we demonstrated a significant increase in ASCT2 mRNA expression in a stepwise pattern in parallel to the increase of malignancy among astrocytomas, confirming previous data. 25 The involvement of ASCT2 in cancer cell proliferation has been confirmed in vitro assay with C6 mouse glioma cell line, 26 and cell line derived from human neuroblastoma. 27 Studies have demonstrated that ASCT2 expression Curves show sensitivity and specificity of ASCT2 expression level in all grades of astrocytomas compared to non--neoplastic brain tissues while LAT1 expression levels show better sensitivity and specificity on more malignant grades of astrocytomas (grade III and IV).…”

Overexpression of ATA1/SLC38A1 Predicts Future Recurrence and Death in Chinese Patients with Hilar Cholangiocarcinoma

“…With the ongoing development in biological research, key molecules involved in several pathways may aid in diagnosing and predicting future recurrence and prognosis [11][12][13][14]. Because of their potential roles in nutrients or energy metabolism of tumor cells, amino acid transporters have become the foci for malignant transformation of mammalian cells, including system A amino acid transporter [15][16][17][18][19].…”

“…Three distinct transporter proteins have been identified that are responsible for system A transport activity in mammalian cells [22]. The three transporters are known as amino acid transporter A (ATA)1, ATA2, and ATA3 [18,23]. These transporters belong to the solute-linked carrier family SLC38 and exhibit differential tissue expression patterns.…”

“…These transporters belong to the solute-linked carrier family SLC38 and exhibit differential tissue expression patterns. Recently, dysregulation of system A members has been described in various human tumor types and cell lines, including primary malignant glioma and hepatocellular cancer [17,18,24]. Nevertheless, it remains unclear whether and how system A might make a functional contribution to the carcinogenesis of hilar cholangiocarcinoma.…”

A metabolic perturbation by U0126 identifies a role for glutamine in resveratrol-induced cell death

“…64,65 As glucose levels in the cell decline, glycosylation is inhibited and plasma membrane levels of growth factor receptors and transporters are reduced, 66 including the glutamine importer ASCT2. Glutamine importers are upregulated in a number of cancer cells lines 67,68 possibly through autocrine growth factor signaling, 69 leading to a glutamine "addiction" phenotype. 11 Loss of glutamine influx may inhibit glutathione, nucleotide, and amino acid synthesis resulting in the induction of autophagy or apoptosis.…”