Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: Involvement of transforming growth factor β1

Takeshi Gohongi, Dai Fukumura, Yves Boucher, Chae Ok Yun, Gerald A. Soff, Carolyn Compton, Takeshi Todoroki, Rakesh K. Jain

Research output: Contribution to journalArticle

Abstract

Angiogenesis inhibitors produced by a primary tumor can create a systemic anti-angiogenic environment and maintain metastatic tumor cells in a state of dormancy. We show here that the gallbladder microenvironment modulates the production of transforming growth factor (TGF)-β1, a multifunctional cytokine that functions as an endogenous anti-angiogenic and antitumor factor in a cranial window preparation. We found that a wide variety of human gallbladder tumors express TGF-β1 irrespective of histologic type. We implanted a gel impregnated with basic fibroblast growth factor or Mz-ChA-2 tumor in the cranial windows of mice without tumors or mice with subcutaneous or gallbladder tumors to study angiogenesis and tumor growth at a secondary site. Angiogenesis, leukocyte-endothelial interaction in vessels and tumor growth in the cranial window were substantially inhibited in mice with gallbladder tumors. The concentration of TGF-β1 in the plasma of mice with gallbladder tumors was 300% higher than that in the plasma of mice without tumors or with subcutaneous tumors. In contrast, there was no difference in the plasma levels of other anti- and pro-angiogenic factors. Treatment with neutralizing antibody against TGF-β1 reversed both angiogenesis suppression and inhibition of leukocyte rolling induced by gallbladder tumors. TGF-β1 also inhibited Mz-ChA-2 tumor cell proliferation. Our results indicate that the production of anti-angiogenesis/proliferation factors is regulated by tumor-host interactions.

Original languageEnglish (US)
Pages (from-to)1203-1208
Number of pages6
JournalNature Medicine
Volume5
Issue number10
DOIs
StatePublished - Oct 1999
Externally publishedYes

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Transforming Growth Factors
Gallbladder
Tumors
Growth
Neoplasms
Angiogenesis Inducing Agents
Plasmas
Leukocyte Rolling
Angiogenesis Inhibitors
Cell proliferation
Fibroblast Growth Factor 2
Neutralizing Antibodies

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gohongi, T., Fukumura, D., Boucher, Y., Yun, C. O., Soff, G. A., Compton, C., ... Jain, R. K. (1999). Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: Involvement of transforming growth factor β1. Nature Medicine, 5(10), 1203-1208. https://doi.org/10.1038/13524

Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth : Involvement of transforming growth factor β1. / Gohongi, Takeshi; Fukumura, Dai; Boucher, Yves; Yun, Chae Ok; Soff, Gerald A.; Compton, Carolyn; Todoroki, Takeshi; Jain, Rakesh K.

In: Nature Medicine, Vol. 5, No. 10, 10.1999, p. 1203-1208.

Research output: Contribution to journalArticle

Gohongi, T, Fukumura, D, Boucher, Y, Yun, CO, Soff, GA, Compton, C, Todoroki, T & Jain, RK 1999, 'Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: Involvement of transforming growth factor β1', Nature Medicine, vol. 5, no. 10, pp. 1203-1208. https://doi.org/10.1038/13524
Gohongi, Takeshi ; Fukumura, Dai ; Boucher, Yves ; Yun, Chae Ok ; Soff, Gerald A. ; Compton, Carolyn ; Todoroki, Takeshi ; Jain, Rakesh K. / Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth : Involvement of transforming growth factor β1. In: Nature Medicine. 1999 ; Vol. 5, No. 10. pp. 1203-1208.
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