Severe pulmonary metastasis in obese and diabetic mice.
Although obesity is known as a risk factor for several human cancers, the association of obesity with cancer recurrence and metastasis remains to be characterized. Here, B16-BL6 melanoma and Lewis lung carcinoma cells were intravenously injected into diabetic (db/db) and obese (ob/ob) mice. The number of experimental lung colonies was markedly promoted in these mice when compared with C57BL/6 mice. In contrast, tumor growth at the implanted site was comparable when cells were inoculated orthotopically. The use of B16-BL6 cells stably transfected with the luciferase gene revealed that the increased metastasis reflected a difference mainly within 6 hr after the intravenous inoculation of tumor cells. Administration of recombinant leptin in ob/ob mice abolished the increase in metastasis early on as well as the decrease in the splenic NK cell number. In addition, depletion of NK cells by an anti-asialo-GM1 antibody abrogated the enhanced metastasis in db/db mice. These results demonstrate that metastasis is markedly promoted in diabetic and obese mice mainly because of decreased NK cell function during the early phase of metastasis.
Mori
Akinori
A
Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
Sakurai
Hiroaki
H
Choo
Min-Kyung
MK
Obi
Ryosuke
R
Koizumi
Keiichi
K
Yoshida
Chiho
C
Shimada
Yutaka
Y
Saiki
Ikuo
I
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000473:pathology; D020738:Leptin / Q000235:genetics / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D018655:Lymphocyte Count; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008820:Mice, Obese; D000077205:Pioglitazone; D011994:Recombinant Proteins / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection
D007004:Hypoglycemic Agents; D020738:Leptin; D011994:Recombinant Proteins; D045162:Thiazolidinediones; D008156:Luciferases; D000077205:Pioglitazone