Prostate carcinoma: production of bioactive factors.
BACKGROUND
Many molecular mechanisms regulate prostate carcinoma pathogenesis, proliferation, and progression to bone metastases. The basic molecular mechanisms are endocrine, paracrine, autocrine, and intracrine. These mechanisms can be mediated by a variety of agents, including gonadal and adrenal steroids, retinoic acid and vitamin D derivatives, neuroendocrine factors, growth factors, cytokines, lymphokine, and bone factors. Prominent among them is parathyroid hormone-related protein (PTHrP).


METHODS
The author studied the expression and regulation of PTHrP production in prostate carcinoma cells with nucleic acid and immunochemical probes for the polypeptide. The robust expression of this oncoprotein by prostate carcinoma has been demonstrated. In the current study the author reviews his results and the studies of other investigators regarding PTHrP and the variety of bioactive factors produced by prostate cells.


RESULTS
PTHrP is expressed by most prostate carcinoma. It also is expressed by normal and hyperplastic prostate cells, and there is a gradient of expression that peaks in malignant prostate cells. PTHrP is processed by carcinoma cells into peptides that have unique biologic effects. Among them are regulation of growth and cytokine expression. It has been observed that the effect of PTHrP can be mediated by novel intracrine pathways in prostate carcinoma. These mechanisms influence transduction of growth regulatory signaling pathways, cell proliferation, immunoregulation, and angiogenesis.


CONCLUSIONS
The current study identified PTHrP among the bioactive prostate factors that appear to participate in prostate carcinoma pathogenesis and progression. This oncofetal protein is commonly expressed by prostate carcinoma, and its regulatory interactions with other bioactive prostate cell products play an important role in the pathobiology of prostate carcinoma. Understanding these regulatory interactions among prostate carcinoma, its cell products, and the skeleton continues to provide insights into the pathogenesis of this disease entity and may provide clues to clinical management.
Deftos
L J
LJ
Department of Medicine, University of California-San Diego and the San Diego Veterans Affairs Medical Center, USA.
D001859:Bone Neoplasms / Q000556:secondary; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D008297:Male; D009389:Neovascularization, Pathologic; D044162:Parathyroid Hormone-Related Protein; D011471:Prostatic Neoplasms / Q000209:etiology*; D011506:Proteins / Q000502:physiology*
D015850:Interleukin-6; D016209:Interleukin-8; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins