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Neuroendocrine and immune mediators in prostate cancer progression.

Cytokines constitute a diverse group of intercellular signaling proteins that regulate local and systemic, immune and inflammatory responses as well as wound healing and hematopoiesis. The proliferation and maturation of cells of the immune system, both normal and malignant, is regulated by cytokines such as the interleukins. Such cytokines may also influence the proliferation and differentiation of other cell types. Prostate epithelial cells differentiate along two pathways, exocrine or neuroendocrine. Elevation in the exocrine marker prostate-specific antigen and/or the neuroendocrine marker chromogranin A in serum has been associated with prostate cancer progression. Interleukin-1 (IL-1) mRNA is expressed by two androgen-insensitive (AI) but not by three androgen-sensitive prostate cancer cell lines. IL-1 inhibits while IL-2 stimulates the growth of the androgen-sensitive LNCaP cell line. Neither affects growth of AI PC-3 or DU-145 cell lines. IL-1 promotes the neuroendocrine phenotype and IL-2 promotes the exocrine phenotype in prostate cancer. The influence of the immune mediators IL-1 and IL-2 on the growth and differentiation of prostate cancer cells and its implication in tumor progression is described herein. Relationship of IL-1 with bone metastasis and the involvement of ss-2 microglobulin in the development and progression of prostate cancer are also discussed.