Increased cystine uptake capability associated with malignant progression of Nb2 lymphoma cells

P. W. Gout, Yujian Kang, D. J. Buckley, N. Bruchovsky, A. R. Buckley

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Analysis of rat, pre-T cell 'Nb2 lymphoma' sublines, manifesting different degrees of malignant progression, can indicate phenotypic changes potentially useful as therapeutic targets. In this study, the prolactin (cytokine)-dependent Nb2-11 and autonomous Nb2-SFJCD1 sublines were compared for in vitro thiol growth requirements. Whereas Nb2-11 culture growth depended on 2-mercaptoethanol (2-ME; 33-100 μM), Nb2-SFJCD1 cells were 2-ME-independent. This difference stemmed from differential uptake of exogenous L-cystine, critically required for proliferation. Uptake of 35S-L-cystine (10 μCi/ml; 40 μM) showed Nb2-11 cells had low cystine uptake capability; 2-ME enhanced cystine uptake to growth-sustaining levels. Nb2-SFJCD1 cells did not require 2-ME due to intrinsic, 11-fold higher cystine uptake via the x-(c) cystine/glutamate transport system. In absence of 2-ME, monosodium glutamate abrogated Nb2-SFJCD1 proliferation by specifically inhibiting cystine uptake (85% at 10 mM). Elevated glutathione (GSH) levels were not essential for growth of either line as shown with L-buthionine-(S,R)-sulfoximine (0.1-4 mM) treatment. The cyst(e)ine requirement therefore did not primarily involve maintenance of normal GSH levels, reported critical for T lymphocyte replication. These and other results suggest increased cystine uptake capability constitutes another potential step in progression of T cell cancers which is not coupled to cytokine autonomy or metastatic ability development. The x-(c) transport system apparently provides a novel target for T cell cancer therapy. Its inhibition would suppress cystine uptake by certain progressed cells, and also interfere with cystine uptake, and subsequent cysteine release, by eg macrophages, thought to have a role in cysteine delivery to lymphoid cells.

Original languageEnglish (US)
Pages (from-to)1329-1337
Number of pages9
JournalLeukemia
Volume11
Issue number8
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Fingerprint

Cystine
Lymphoma
Mercaptoethanol
Growth
T-Lymphocytes
Cysteine
Cytokines
Sodium Glutamate
T-Cell Lymphoma
Cell- and Tissue-Based Therapy
Sulfhydryl Compounds
Prolactin
Glutathione
Cysts
Glutamic Acid
Neoplasms
Macrophages
Maintenance
Lymphocytes

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Increased cystine uptake capability associated with malignant progression of Nb2 lymphoma cells. / Gout, P. W.; Kang, Yujian; Buckley, D. J.; Bruchovsky, N.; Buckley, A. R.

In: Leukemia, Vol. 11, No. 8, 01.01.1997, p. 1329-1337.

Research output: Contribution to journalArticle

Gout, P. W. ; Kang, Yujian ; Buckley, D. J. ; Bruchovsky, N. ; Buckley, A. R. / Increased cystine uptake capability associated with malignant progression of Nb2 lymphoma cells. In: Leukemia. 1997 ; Vol. 11, No. 8. pp. 1329-1337.
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