Man has been found to produce highly conserved chitinases. The most prominent is the phagocyte-derived chitotriosidase, the plasma levels of which are markedly elevated in some pathological conditions. Here, we report that both polymorphonuclear neutrophils (PMNs) and macrophages (m) are a source of chitotriosidase. The enzyme is located in specific granules of human PMNs and secreted following stimulation with granulocyte macrophage colony-stimulating factor (GM-CSF). In addition, GM-CSF induces expression of chitotriosidase in m that constitutively secrete the enzyme and partly accumulate it in their lysosomes. Studies with recombinant human chitotriosidase revealed that the enzyme targets chitin-containing fungi. These findings are consistent with earlier observations concerning anti-fungal activity of homologous plant chitinases and beneficial effects of GM-CSF administration in individuals suffering from invasive fungal infections. In conclusion, chitotriosidase should be viewed as a component of the innate immunity that may play a role in defence against chitin-containing pathogens and the expression and release of which by human phagocytes is highly regulated.

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BACKGROUND.The most common site of metastases in prostate cancer is the skeleton and occurs in 70-80% of patients with prostate carcinoma. Calciotrophic peptides are important in the growth and development of normal bone matrix. METHODS. Three human prostate carcinoma cells lines, DU-145, PC-3, and LNCaP, were exposed to varying concentrations of parathyroid hormone (PTH) or calcitonin (CT). Cell proliferation and chemotaxis were assessed. RESULTS. Proliferation increased in LNCaP cells in a dose-dependent manner following treatment with PTH. Proliferation was not altered in PC-3 cells in response to PTH. Proliferation was decreased in DU-145 and PC-3 cells and increased in LNCaP cells after treatment with CT. Cell chemotaxis was increased in the presence of PTH in DU-145 and PC-3 cells compared to vehicle-treated controls. CONCLUSIONS. The combined proliferation and chemotaxis data suggest that PTH has a dual role in prostate carcinoma resulting in an increase in the number and migration of selected prostate cancer cells. With CT, chemotaxis was unchanged in the DU-145 and PC-3 cells and significantly elevated in the LNCaP cell line. The calciotrophic hormones, PTH and CT, may play an integral role in the regulation of prostate cell growth and metastases.

The extensive mortality and morbidity associated with prostate cancer is caused by the high prevalence of metastatic disease at the time of diagnosis. The area most frequently involved in metastatic prostate cancer is the skeleton. Unlike other cancers, which metastasize to bone and destroy the bone matrix, prostate cancer is unique in that it is osteogenic, resulting in the formation of dense, sclerotic bone with high levels of osteoblastic activity. We proposed that factors produced by bone cells may be responsible for the development of prostate carcinoma metastasis. We studied the effects of these growth factors on prostate cell proliferation by [3H]thymidine incorporation and chemotaxis by the double-filter chamber method. Three prostate carcinoma cell lines were studied, LNCaP (androgen responsive) and PC-3 and DU-145 (androgen unresponsive). The bone-associated growth factors tested were: insulin-like growth factors I and II (IGF-I, IGF-II), transforming growth factor beta, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha), IGF-I and IGF-II significantly increased proliferation in all three cell lines, whereas IL-6, TNF-alpha, and IL-1 beta significantly decreased proliferation. Transforming growth factor beta induced a biphasic response in proliferation in DU-145 and PC-3 cells and produced no response on LNCaP cells. Increased cell chemotaxis occurred in the presence of IGF-I and IGF-II, and decreased cell chemotaxis occurred with the addition of TNF-alpha and IL-1 beta. These data indicate that growth factors produced by bone cells alter prostate carcinoma cell proliferation and chemotaxis and suggest that modulations of the production of these factors may be a potential therapeutic intervention in deterring the metastasis of prostate carcinoma to bone.

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