TGF-beta signalling-related markers in cancer patients with bone metastasis

Biomarkers. 2008 Mar;13(2):217-36. doi: 10.1080/13547500701676019.


We measured transforming growth factor (TGF)-beta-dependent biomarkers in plasma and in peripheral blood mononuclear cells (PBMCs) to identify suitable pharmacodynamic markers for future clinical trials with TGF-beta inhibitors. Forty-nine patients with bone metastasis were enrolled in the study, including patients with breast (n=23) and prostate cancer (n=15). Plasma TGF-beta1 levels were elevated in more than half of the cancer patients (geometric mean 2.63 ng ml(-1)) and positively correlated with increased platelet factor 4 (PF4) levels, parathyroid-related protein (PTHrP), von Willebrand Factor (vWF) and interleukin (IL)-10. PBMC were stimulated ex vivo to determine the individual biological variability of an ex vivo assay measuring pSMAD expression. This assay performed sufficiently well to allow its future use in a clinical trial of a TGF-beta inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers
  • Bone Neoplasms / blood
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-11 / blood
  • Male
  • Middle Aged
  • Parathyroid Hormone-Related Protein / blood
  • Platelet Factor 4 / blood
  • Signal Transduction
  • Smad Proteins / blood
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / blood*


  • Biomarkers
  • Interleukin-11
  • Parathyroid Hormone-Related Protein
  • Smad Proteins
  • Transforming Growth Factor beta
  • Platelet Factor 4