Cancer cells release glutamate via the cystine/glutamate antiporter.
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.
Sharma
Mohit K
MK
Department of Pathology & Molecular Medicine, McMaster University, Ont, Canada.
Seidlitz
Eric P
EP
Singh
Gurmit
G
D027182:Amino Acid Transport System y+ / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D027341:Excitatory Amino Acid Transporter 1 / Q000096:biosynthesis* / Q000235:genetics; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis* / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D050598:Vesicular Glutamate Transport Protein 1 / Q000096:biosynthesis* / Q000235:genetics
D027182:Amino Acid Transport System y+; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D012333:RNA, Messenger; C493464:SLC17A7 protein, human; C493394:SLC1A3 protein, human; C118895:SLC7A11 protein, human; D050598:Vesicular Glutamate Transport Protein 1; D018698:Glutamic Acid