PTHrP and Lung Cancer

Parathyroid hormone-related protein (PTHrP) is a paraneoplastic protein that is expressed in roughly two-thirds of all non-small lung carcinomas (NSCLC). The receptor for PTHrP is frequently present in lung cancers and is also made in pulmonary endothelial cells and other cells derived from normal lung. PTHrP exerts effects on cell growth, apoptosis and invasiveness. For example, Dr. Hastings has found that PTHrP modifies the sensitivity of lung cancer cells to apoptotic stimuli through a protein kinase A-dependent mechanism. PTHrP regulation cancer cell growth and survival functions could influence cancer progression, a prospect that has been supported by animal and patient studies in Dr. Hastings' laboratory. In a mouse orthotopic lung carcinoma model, tumors grow more rapidly in mice treated with a neutralizing antibody to lower endogenous PTHrP levels, suggesting that the hormone inhibits lung carcinoma growth. In patients with non-small cell lung carcinoma, tumor PTHrP expression is associated with longer survival (click for a micrograph of lung carcinomas with PTHrP immunoreactivity) consistent with an inhibitory effect of PTHrP on cancer. Interestingly, the protective effect of PTHrP occurs only in women, not in men. Studies are ongoing to determine how the hormone slows tumor growth, why it affects survival and why the effect is sex-dependent.

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Email Randolph H. Hastings, M.D., Ph.D.: rhhastings@ucsd.edu
   

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