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Evidence for control of nitric oxide synthesis by intracellular transforming growth factor-beta1 in tumor cells.

P Lagadec1, S Raynal, B Lieubeau

  • 1Cancer Immunotherapy Research Laboratory, Ecole Pratique des Hautes Etudes, INSERM U517, France. lagadecp@satie.u-bourgogne.fr

The American Journal of Pathology
|June 11, 1999
PubMed

Insights

Transforming growth factor-beta1 (TGF-beta1) suppresses nitric oxide (NO) production in colon carcinoma cells. Inhibiting TGF-beta1 may offer a new strategy for developing antitumoral agents by boosting NO levels.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Transforming growth factor-beta1 (TGF-beta1) typically down-regulates nitric oxide (NO) synthesis in normal cells.
  • The role of TGF-beta1 in modulating NO production within tumor cells and its impact on tumor development requires further investigation.

Purpose of the Study:

  • To investigate the influence of TGF-beta1 on NO production in colon carcinoma cells.
  • To explore the consequences of this interaction for tumor development and potential therapeutic strategies.

Main Methods:

  • Monitoring intratumoral concentrations of TGF-beta1 and NO during the growth of PROb colon carcinoma cells in BDIX rats.
  • Analyzing changes in TGF-beta1 and NO levels following tumor regression induced by lipid A injections.
  • Utilizing PROb cells transfected with TGF-beta1 antisense mRNA and employing neutralizing antibodies against the TGF-beta type II receptor to assess NO secretion mechanisms.

Main Results:

  • Intratumoral TGF-beta1 increased while NO levels remained low during PROb tumor growth.
  • Tumor regression was associated with decreased TGF-beta1 and increased NO.
  • PROb cells were identified as the source of both NO and TGF-beta1.
  • In vitro studies demonstrated an inverse correlation between TGF-beta1 secretion and NO production, mediated by an intracellular mechanism.

Conclusions:

  • Endogenous TGF-beta1 down-regulates NO synthesis in PROb colon carcinoma cells via an intracellular pathway.
  • Targeting endogenous TGF-beta1 presents a potential therapeutic strategy for developing novel antitumoral agents by modulating NO production.

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