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Glutamine metabolism is well-established to contribute to cancer cell growth and proliferation by providing a source of nitrogen for nucleotide and amino acid biosynthesis as well as TCA cycle intermediates. There is also accumulating evidence that glutamine metabolism may contribute to metastasis although mechanistic links to tumour cell migration and invasion remain unclear. We have generated a number of highly invasive primary cell lines from the polyoma middle-T genetically engineered mouse model of breast cancer (MMTV-PyMT) and found that withdrawal of glutamine from these cells reduces not only their proliferation, but also their invasive migration into 'stroma-like' preparations of fibroblast-derived extracellular matrix. Our metabolomic analyses indicate that invasive MMTV-PyMT cells actively secrete glutamate, a product of glutamine metabolism, into the extracellular milieu. Moreover, addition of …