Cancer Cell Biology
Severe pulmonary metastasis in obese and diabetic mice
Version of Record online: 22 SEP 2006
Copyright © 2006 Wiley-Liss, Inc.
International Journal of Cancer
Volume 119, Issue 12, pages 2760–2767, 15 December 2006
How to Cite
Mori, A., Sakurai, H., Choo, M.-K., Obi, R., Koizumi, K., Yoshida, C., Shimada, Y. and Saiki, I. (2006), Severe pulmonary metastasis in obese and diabetic mice. Int. J. Cancer, 119: 2760–2767. doi: 10.1002/ijc.22248
- Issue online: 26 OCT 2006
- Version of Record online: 22 SEP 2006
- Manuscript Accepted: 10 JUL 2006
- Manuscript Received: 21 MAR 2006
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- ONO Medical Research Foundation
- NK cell;
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. © 2006 Wiley-Liss, Inc.