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Related Experiment Videos

Selective decrease of SN1(SNAT3) mRNA expression in human and rat glioma cells adapted to grow in acidic medium.

Marta Sidoryk1, Marta Obara, Jan Albrecht

  • 1Department of Neurotoxicology, Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Pawińskiego St. 5, Poland.

Neurochemistry International
|March 4, 2006
PubMed
Summary

System N glutamine transporter SN1(SNAT3) is overexpressed in malignant gliomas. However, this study found that acidic conditions decrease SN1(SNAT3) mRNA expression in glioma cells, suggesting it is not involved in adapting to the acidic tumor microenvironment.

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Physiology

Background:

  • System N glutamine transporter SN1(SNAT3) is overexpressed in malignant glioma cells.
  • The role of SN1(SNAT3) in glioma growth and adaptation to the tumor microenvironment is unknown.
  • Acidification of the extracellular space is a common feature of glial tumors.

Purpose of the Study:

  • To investigate the role of SN1(SNAT3) and other glutamine transporters in glioma cell adaptation to acidic conditions.
  • To determine if SN1(SNAT3) expression or function is affected by extracellular acidity.

Main Methods:

  • Human (T98G) and rat (C6) glioma cells were incubated in acidic medium (pH 6.5).
  • Messenger RNA (mRNA) expression of glutamine transporters (SN1(SNAT3), ASCT2, ATA1, SN2(SNAT5)) was measured.

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  • Cell viability was assessed using MTT assay, and intracellular pH was measured using a fluorescent probe (BCECF-AM).
  • Glutamine uptake was measured using [(3)H]Gln.
  • Main Results:

    • Glioma cells adapted to acidic conditions, maintaining a slightly alkaline intracellular pH without significant cell loss.
    • Acidic conditions significantly decreased SN1(SNAT3) mRNA expression in both T98G and C6 cells.
    • Expression of other glutamine transporters (ASCT2, ATA1, SN2(SNAT5)) remained unaffected by acidic conditions.
    • Total glutamine uptake was not affected by acidic conditions, and the system N-mediated component was only slightly decreased.
    • System ASCT2 mediated the majority of glutamine uptake in glioma cells.

    Conclusions:

    • SN1(SNAT3) is unlikely to be involved in the adaptation of cultured glioma cells to an acidic milieu.
    • The observed decrease in SN1(SNAT3) expression under acidic conditions suggests a downregulation rather than an adaptive role.
    • Further research is needed to elucidate the specific functions of SN1(SNAT3) in glioma progression.