Growth of HPV-18 immortalized human prostatic intraepithelial neoplasia cell lines. Influence of IL-10, follistatin, activin-A, and DHT.

Wang, M; Liu, A; Garcia, Fernando U.; Rhim, J. S.; Stearns, Mark E.

doi:10.3892/ijo.14.6.1185

Cited by 13 publications

(9 citation statements)

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“…However, it is unknown which prostate cancer-derived factors may be involved in this phenomenon. A variety of tumours, including prostate cancer (Stearns and Wang, 1998;Sharma et al, 1999;Stearns et al, 1999;Wang et al, 1999), have been shown to release IL-10, a cytokine that could enhance the spontaneous apoptosis in DC (Ludewig et al, 1995). TGF-β is another candidate cytokine, which has been shown to be released by prostate cancer cells (Burchardt et al, 1999;Wikstrom et al, 1999;Cardillo et al, 2000) and might affect DC as well (Caux et al, 1999;Strobl and Knapp, 1999).…”

Section: Discussionmentioning

confidence: 99%

Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins

et al. 2000

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Summary Prostate cancer is the most common cancer in men in the United States, and second in cancer-induced mortality. It is likely that tumour-induced immunosuppression is one of the reasons for low treatment efficacy in patients with advanced prostate cancer. It has been recently demonstrated that prostate cancer tissue is almost devoid of dendritic cells (DC), the major antigen-presenting cells responsible for the induction of specific antitumour immune responses. In this study, we have tested the hypothesis that prostate cancer induces progressive suppression of the DC system. We found that co-incubation of human DC with three prostate cancer cell lines led to the high levels of premature apoptosis of DC, which were significantly higher than in DC cultures co-incubated with normal prostate cells or blood leucocytes. Stimulation of DC for 24 hours with CD40 ligand (CD154), IL-12 or IL-15 prior to their co-incubation with prostate cancer cells resulted in a significant increase in DC survival in the tumour microenvironment. Furthermore, activation of DC with these cytokines was also accompanied by increased expression of the anti-apoptotic protein Bcl-x L in DC, suggesting a possible mechanism involved in DC protection from apoptotic death. In summary, our data demonstrate that prostate cancer induces active elimination of DC in the tumour microenvironment. Stimulation of DC by CD154, IL-12 or IL-15 leads to an increased expression of the anti-apoptotic protein Bcl-x L and increased resistance of DC to prostate cancer-induced apoptosis. These results suggest a new mechanism of tumour escape from immune recognition and demonstrate the cytokinebased approaches which might significantly increase the efficacy of DC-based therapies for cancer. (2000) 83(4), 506-513 © 2000 Cancer Research Campaign doi: 10.1054/ bjoc.2000.1289, available online at http://www.idealibrary.com on immunologic response of the host and allowing tumour to progress (Shurin, 1999).When it was generally accepted that DC play a major role in the induction and development of specific immunologic responses, several clinical trials were initiated which used DC-based immunotherapies to treat cancer patients, including patients with prostatic carcinomas. For instance, Salgaller et al (1998) treated prostate cancer patients using DC pulsed with prostate membrane specific antigen (PMSA)-associated peptides. The results of this and similar clinical trials were quite optimistic. However, presence of patients with limited or no responses suggests that immunobiology of DC in in vivo tumour microenvironment might be different from our expectations and indicates the actual need for the improvement of modern DC-based immunotherapies. We hypothesized that one of the reasons for the limited efficacy of the immune responses in treated patients may be the prostate cancerinduced suppression and elimination of DC.Premature apoptosis of DC, induced by different tumour cell lines, has been described early (Esche et al, 1999). However, signal transduction pathways...

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Section: Discussionmentioning

confidence: 99%

Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins

et al. 2000

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“…PIN cells are thus an important cell line for the investigation of oncogenic processes and molecules in a premalignant context. Developed and introduced into the literature in 1999 by Stearns and colleagues, this is a line isolated from an African-American patient [89]. The same HPV-18 construct used to immortalize RWPE-1 cells was also used to immortalize this cell line.…”

Section: Non-tumor Prostatic Epithelial Linesmentioning

confidence: 99%

In vitro and in vivo model systems used in prostate cancer research

2015

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New incidence of prostate cancer is a major public health issue in the Western world, and has been rising in other areas of the globe in recent years. In an effort to understanding the molecular pathogenesis of this disease, numerous cell models have been developed, arising mostly from patient biopsies. The introduction of the genetically engineered mouse in biomedical research has allowed the development of murine models that allow for the investigation of tumorigenic and metastatic processes. Current challenges to the field include lack of an animal model that faithfully recapitulates bone metastasis of prostate cancer.

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“…65,66 This cartilage protective activity most likely adds to the effect of p21Cip1 in IL-4-and IL-10-mediated growth arrest and inhibition of proliferation ( Figure 7). [67][68][69][70] Besides p16INK4, the p33ING1 gene, a potential tumor suppressor gene which inhibits cellular growth in various tissues, 71 is up-regulated in RA synovial fibroblasts after double gene transfer.…”

Section: Figure 6 Immunohistochemistry For Human Activin and Follistamentioning

confidence: 99%

Inhibition of cartilage destruction by double gene transfer of IL-1Ra and IL-10 involves the activin pathway

et al. 2002

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Growth of HPV-18 immortalized human prostatic intraepithelial neoplasia cell lines. Influence of IL-10, follistatin, activin-A, and DHT.

Cited by 13 publications

References 0 publications

Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins

Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins

In vitro and in vivo model systems used in prostate cancer research

Inhibition of cartilage destruction by double gene transfer of IL-1Ra and IL-10 involves the activin pathway

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