STAT3 activation regulates growth, inflammation, and vascularization in a mouse model of gastric tumorigenesis

Gastroenterology. 2006 Oct;131(4):1073-85. doi: 10.1053/j.gastro.2006.07.018. Epub 2006 Jul 24.


Background & aims: The gp130(757F/F) mouse is a well-characterized and robust model of distal gastric tumorigenesis displaying many of the characteristics of human intestinal type gastric cancer. Key to the development of tumors in this model, and in many examples of human tumor development, is hyperactivation of the transcription factor STAT3. This study addressed the requirement for STAT3 activation in tumor initiation and characterized some of the genes downstream of STAT3 required for tumor development. Furthermore, the interaction among STAT3, the microbial environment, and tumorigenesis was evaluated.

Methods: The role of STAT3 in gastric tumor development was assessed in detail in gp130(757F/Y757F):STAT3(+/-) mice displaying reduced STAT3 activity. Tumor size was quantified morphologically, and the effects on endocrine cell populations, neovascularization, and inflammatory cell infiltration as well as the outcome of STAT3 activation on transcription of a number of genes relevant in growth and inflammation were quantified.

Results: Loss of one STAT3 allele in gp130(757F/F) mice reduced the frequency and rate of tumor development because of inhibition of proliferation-induced glandular hyperplasia. There was also a concomitant reduction in the degree of inflammatory infiltration and cytokine and chemokine expression, angiogenesis, and expression of metalloproteinases and growth factors. Antimicrobial treatment of gp130(757F/F) mice slowed tumor growth coincident with reduced macrophage and neutrophil infiltration.

Conclusions: Activation of STAT3 and the microbial environment are pivotal for gastric tumor initiation and development in the gp130(757F/F) mouse, thus supporting the notion that STAT3 activation may play a role in human gastric cancer development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division
  • Cell Movement / immunology
  • Cytokine Receptor gp130 / genetics
  • Disease Models, Animal
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Gastric Mucosa / blood supply
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gastrins / genetics
  • Gastrins / metabolism
  • Gastritis / immunology
  • Gastritis / pathology
  • Gastritis / physiopathology*
  • Gene Expression Regulation, Neoplastic
  • Leptin / genetics
  • Leptin / metabolism
  • Macrophages, Peritoneal / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / physiopathology*
  • Neutrophils / immunology
  • Phosphorylation
  • Pyloric Antrum / blood supply
  • Pyloric Antrum / metabolism
  • Pyloric Antrum / pathology
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / immunology
  • STAT3 Transcription Factor / metabolism*
  • Somatostatin / genetics
  • Somatostatin / metabolism
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / physiopathology*


  • Gastrins
  • Leptin
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Cytokine Receptor gp130
  • Somatostatin