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Cancer cells release glutamate via the cystine/glutamate antiporter
Authors:Mohit K. Sharma  Gurmit Singh
Affiliation:Department of Pathology & Molecular Medicine, McMaster University, Ont., Canada Research Department, Juravinski Cancer Centre, Hamilton, Ont., Canada
Abstract:Although the amino acid glutamate is used as an intercellular signaling molecule for normal bone homeostasis, little is known regarding its possible role in the metabolic disruption characteristic of bone metastasis. We have previously shown in vitro that cancer cell lines relevant to bone metastasis release glutamate into the extracellular environment. This study demonstrates the expression of multiple glutamate transporters in cancer cell lines of non-central nervous system origin. Furthermore, we identify the molecular mechanism responsible for glutamate export and show that this system can be inhibited pharmacologically. By highlighting that glutamate secretion is a common biological feature of cancer cells, this study suggests that tumor-derived glutamate could interfere with glutamate-dependent intercellular signaling in normal bone. Pharmacological interference with cancer cell glutamate release may be a viable option for limiting host bone response to invading tumor cells in bone metastasis.
Keywords:CNS, central nervous system   EAAT1, excitatory amino acid transporter 1   EAAT2, excitatory amino acid transporter 2   GLAST-1, glutamate/aspartate transporter 1   GLT-1, glutamate transporter 1   VGLUT1, vesicular glutamate transporter 1   xCT, light-chain subunit of system xc&minus   glutamate/cystine antiporter
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