Glutamine targeting inhibits systemic metastasis in the VM-M3 murine tumor model.
Metastatic cancer is a major cause of morbidity and mortality. Current therapeutic options consist of chemotherapy, radiation or targeted therapies. However, these therapies are often toxic, effective over a small range of cancer types or result in drug resistance. Therefore, a more global, less toxic strategy for the management of metastatic cancer is required. Although most cancers display increased glucose metabolism, glutamine is also a major energy substrate for many cancers. We evaluated the antimetastatic potential of 6-diazo-5-oxo-L-norleucine (DON), a glutamine analog, using the new VM mouse model of systemic metastasis. We found that primary tumor growth was ∼20-fold less in DON-treated mice than in untreated control mice. We also found that DON treatment inhibited metastasis to liver, lung and kidney as detected by bioluminescence imaging and histology. Our findings provide proof of concept that metabolic therapies targeting glutamine metabolism can manage systemic metastatic cancer.
Shelton
Laura M
LM
Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
Huysentruyt
Leanne C
LC
Seyfried
Thomas N
TN
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D031204:Caloric Restriction; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D054022:Cerebrum / Q000378:metabolism / Q000473:pathology; D003980:Diazooxonorleucine / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005260:Female; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D005973:Glutamine / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis
D000964:Antimetabolites, Antineoplastic; D001786:Blood Glucose; D003980:Diazooxonorleucine; D005973:Glutamine; D005947:Glucose
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