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Malignant cells, directors of the malignant process: role of transforming growth factor-beta

B A Teicher1

  • 1Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. _teicher_beverly_a@lilly.com

Cancer Metastasis Reviews
|February 8, 2002
PubMed

Insights

Malignant cells evade growth control by altering transforming growth factor-beta (TGF-beta) signaling. This manipulation promotes cancer progression, immune suppression, and drug resistance, suggesting TGF-beta pathway inhibition as a therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Malignant cells exhibit altered growth and invasion programs.
  • Loss of response to transforming growth factor-beta (TGF-beta) is a key event in cancer evolution, often due to mutations in TGF-beta receptors or Smad proteins.

Purpose of the Study:

  • To investigate the role of TGF-beta in cancer survival, invasion, and immune evasion.
  • To explore the therapeutic potential of targeting the TGF-beta pathway in various cancers.

Main Methods:

  • Analysis of TGF-beta signaling pathways in malignant cells.
  • Clinical observation of TGF-beta levels in cancer patients.
  • Preclinical studies using in vivo cancer models (e.g., breast, prostate, xenografts).

Main Results:

  • Malignant cells secrete TGF-beta, which suppresses anti-tumor immunity, enhances extracellular matrix production, and promotes angiogenesis.
  • Elevated TGF-beta levels are observed in patients with breast, lung, liver, and prostate cancers.
  • TGF-beta dysregulation correlates with increased tumorigenicity, invasion, and drug resistance in preclinical models.

Conclusions:

  • TGF-beta plays a critical role in cancer progression and immune evasion, mimicking developmental processes.
  • Targeting TGF-beta signaling, in combination with cytotoxic therapies, offers a promising strategy for cancer treatment.

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