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

• Published in: Biomarkers 2008-03, Vol.13 (2), p.217-236
• Main Authors: Baselga, Jose, Rothenberg, Mace L., Tabernero, Josep, Seoane, Joan, Daly, Thomas, Cleverly, Ann, Berry, Brandi, Rhoades, Susanne K., Ray, Chad A., Fill, Jeffrey, Farrington, Daphne L., Anne Wallace, Lisa, Yingling, Jonathan M., Lahn, Michael, Arteaga, Carlos, Carducci, Michael
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Biomarkers; Bone Neoplasms - blood; Bone Neoplasms - drug therapy; Bone Neoplasms - secondary; cancer; Diseases of the osteoarticular system; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-11 - blood; Male; Medical sciences; Middle Aged; Parathyroid Hormone-Related Protein - blood; plasma biomarkers; Platelet Factor 4 - blood; Signal Transduction; Smad Proteins - blood; TGF-β; Transforming Growth Factor beta - antagonists & inhibitors; Transforming Growth Factor beta - blood; Tumors of striated muscle and skeleton
• ISSN: 1354-750X; 1366-5804
• DOI: 10.1080/13547500701676019

We measured transforming growth factor (TGF)-β-dependent biomarkers in plasma and in peripheral blood mononuclear cells (PBMCs) to identify suitable pharmacodynamic markers for future clinical trials with TGF-β 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-β1 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-β inhibitor.