Proliferation-dependent changes in amino acid transport and glucose metabolism in glioma cell lines Journal Article


Authors: Sasajima, T.; Miyagawa, T.; Oku, T.; Gelovani, J. G.; Finn, R.; Blasberg, R.
Article Title: Proliferation-dependent changes in amino acid transport and glucose metabolism in glioma cell lines
Abstract: Amino acid imaging is increasingly being used for assessment of brain tumor malignancy, extent of disease, and prognosis. This study explores the relationship between proliferative activity, amino acid transport, and glucose metabolism in three glioma cell lines (U87, Hs683, C6) at different phases of growth in culture. Growth phase was characterized by direct cell counting, proliferation index determined by flow cytometry, and [3H]thymidine (TdR) accumulation, and was compared with the uptake of two non-metabolized amino acids ([14C]aminocyclopentane carboxylic acid (ACPC) and [ 14C]aminoisobutyric acid (AIB)), and [18F]fluorodeoxy- glucose (FDG). Highly significant relationships between cell number (density), proliferation index, and TdR accumulation rate were observed in all cell lines (r>0.99). Influx (K1) of both ACPC and AIB was directly related to cell density, and inversely related to the proliferation index and TdR accumulation in all cell lines. The volume of distribution (Vd) for ACPC and AIB was lowest during rapid growth and highest during the near-plateau growth phase in all cell lines. FDG accumulation in Hs683 and C6 cells was unaffected by proliferation rate, growth phase, and cell density, whereas FDG accumulation was correlated with TdR accumulation, growth phase, and cell density in U87 cells. This study demonstrates that proliferation rate and glucose metabolism are not necessarily co-related in all glioma cell lines. The values of K1 and Vd for ACPC and AIB under different growth conditions suggest that these tumor cell lines can up-regulate amino acid transporters in their cell membranes when their growth conditions become adverse and less than optimal.
Keywords: controlled study; human cell; flow cytometry; glioma; radiopharmaceuticals; tumor proliferation; cell proliferation; cell cycle; cancer cell culture; cell line, tumor; glioma cell; cell membrane; fluorodeoxyglucose f 18; fluorodeoxyglucose f18; cellular distribution; imaging; malignant neoplastic disease; metabolic clearance rate; cell count; amino acid; glucose; cell density; cell level; thymidine; amino acid transport; tritium; glucose metabolism; carbon 14; radiation detector; gliomas; cyclopentanes; pentetate technetium tc 99m; amino acid transport systems; growth curve; carbon radioisotopes; 2 amino 2 methylpropionic acid; cycloleucine; aminoisobutyric acids; humans; prognosis; human; article; 18f-fluorodeoxyglucose; non-metabolized amino acid transport; amino acid transporter
Journal Title: European Journal of Nuclear Medicine and Molecular Imaging
Volume: 31
Issue: 9
ISSN: 1619-7070
Publisher: Springer  
Date Published: 2004-09-01
Start Page: 1244
End Page: 1256
Language: English
DOI: 10.1007/s00259-004-1512-2
PROVIDER: scopus
PUBMED: 15141325
DOI/URL:
Notes: Eur. J. Nucl. Med. Mol. Imaging -- Cited By (since 1996):26 -- Export Date: 16 June 2014 -- CODEN: EJNMA -- Source: Scopus
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MSK Authors
  1. Juri Gelovani
    125 Gelovani
  2. Ronald G Blasberg
    272 Blasberg
  3. Ronald D Finn
    279 Finn