Severe pulmonary metastasis in obese and diabetic mice

Int J Cancer. 2006 Dec 15;119(12):2760-7. doi: 10.1002/ijc.22248.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung / genetics
  • Carcinoma, Lewis Lung / metabolism
  • Carcinoma, Lewis Lung / pathology*
  • Cell Line, Tumor
  • Hypoglycemic Agents / pharmacology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / pathology
  • Leptin / genetics
  • Leptin / pharmacology
  • Luciferases / genetics
  • Luciferases / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary*
  • Lymphocyte Count
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology*
  • Mice
  • Mice, Obese
  • Pioglitazone
  • Recombinant Proteins / pharmacology
  • Thiazolidinediones / pharmacology
  • Time Factors
  • Transfection


  • Hypoglycemic Agents
  • Leptin
  • Recombinant Proteins
  • Thiazolidinediones
  • Luciferases
  • Pioglitazone