Tumor–host interactions in the gallbladder suppress distal angiogenesis and tumor growth: Involvement of transforming growth factor β1 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-10

AUTHORS

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

ABSTRACT

Angiogenesis inhibitors produced by a primary tumor can create a systemic anti-angiogenic environment and maintain metastatic tumor cells in a state of dormancy1,2. 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 anti-tumor 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 factor3 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. More... »

PAGES

1203-1208

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/13524

DOI

http://dx.doi.org/10.1038/13524

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042429861

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10502827


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