Epidermal growth factor, neurotrophins and the metastatic cascade in prostate cancer.
Although cancer of the prostate (CaP) is the most commonly occurring cancer in males, there are major limitations in its diagnosis and long-term cure. Consequently, understanding the molecular mechanisms involved in the progression of CaP is of particular importance for production of pharmacological and biological agents to manage the disease. The development of the normal prostate is regulated by stromal-epithelial interactions via endocrine and paracrine factors, such as androgens and growth factors, which act as precise homeostatic regulators of cellular proliferation. Importantly, after a period of hormonal therapy, CaP shifts from an androgen-dependent to an androgen-independent state with a concomitant switch from paracrine to autocrine growth factor stimulation and subsequent upregulation of growth factor expression. Thus, growth factors and their receptors have a pivotal role in CaP. This is emphasized by current evidence obtained from clinical specimens as well as several in vitro and in vivo models strongly suggesting that epidermal growth factor and the neurotrophins (nerve growth factor, brain derived neurotrophin factor, neurotrophin-3 and neurotrophin-4/5) together with their tyrosine kinase receptors could play a very significant role in CaP progression.
Department of Biological Sciences, Molecular Signalling Group, Neuroscience Solution to Cancer Research Group, Imperial College London, Sir Alexander Fleming Building, Exhibition Road, London SW7 2AZ, UK. x.montano@imperial.ac.uk
Ximena
X
Montano
Mustafa B A
MB
Djamgoz
D000728:Androgens / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D002455:Cell Division; D004815:Epidermal Growth Factor / Q000502:physiology*; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009414:Nerve Growth Factors / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D017154:Stromal Cells / Q000473:pathology
D000728:Androgens; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D004815:Epidermal Growth Factor