Neuropeptides, apoptosis and ion changes in prostate cancer. Methods of study and recent developments.
It has been suggested that neuroendocrine (NE) cells provide paracrine stimuli for the propagation of local carcinoma cells and that NE differentiation is associated with the progression of prostate cancer toward an androgen-independent state. Apoptosis comprises a critical intracellular defense mechanism against tumorigenic growth and is associated with a number of changes in the elemental content of the cell. The neuropeptides bombesin and calcitonin, which inhibit etoposide-induced apoptosis, also inhibit the etoposide-induced elemental changes in prostate carcinoma cells. This important fact strengthens the link between apoptosis and changes in the intracellular elemental content. This protective effect on etoposide-induced apoptosis appears to be quite similar in androgen-dependent and androgen-independent cell lines. This confirms that neuropeptides confer antiapoptotic capabilities on non-neuroendocrine cells in close proximity to neuroendocrine cells. It can therefore be speculated that certain neuroendocrine peptides can increase the survival and further growth of neighboring cells and may thereby contribute to the aggressive clinical course of prostate tumors containing neuroendocrine elements. In addition, this correlation provides an objective basis for the study of neuropeptide target points and may be helpful for alternative therapeutic protocols using neuropeptide inhibitors in the treatment of patients with advanced prostatic carcinoma. The culture techniques described were, thus, designed in order to achieve two important goals. First, the development of an in vitro model that allows an approach to neuroendocrine differentiation in prostate cancer and its role in apoptosis blockage. Second, the method has been designed in order to permit rapid cryofixation of intact cell monolayers for subsequent x-ray microanalysis.
Vilches
J
J
Department of Cell Biology, School of Medicine, University of Cádiz, Cádiz, Spain. jose.vilches@uca.es
Salido
M
M
Fernández-Segura
E
E
Roomans
G M
GM
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004577:Electron Probe Microanalysis; D006801:Humans; D007477:Ions / Q000378:metabolism*; D008297:Male; D008855:Microscopy, Electron, Scanning; D009479:Neuropeptides / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure
D007477:Ions; D009479:Neuropeptides