Interferon‐γ induces neuroendocrine‐like differentiation of human prostate basal‐epithelial cells

Untergasser, Gerold; Plas, Eugen; Pfister, Gerald; Heinrich, Elmar; Berger, Peter

doi:10.1002/pros.20261

Cited by 19 publications

(10 citation statements)

References 43 publications

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“…Further break-down of these CT signature genes on the basis of their function, revealed that 13 genes were associated with cell-cell adhesion and six genes were associated with inflammation, suggesting that inflammation and loss of cell-cell adhesion may be early responses of PC cells and may constitute early events associated with CT-mediated metastasis. These results are consistent with proinflammatory phenotype of human PC stem cells, further supporting a possible role of CT-CTR axis in maintaining stemness of PC cells (Untergasser et al 2005, Birnie et al 2008.…”

Section: Discussionsupporting

confidence: 85%

Calcitonin promotes in vivo metastasis of prostate cancer cells by altering cell signaling, adhesion, and inflammatory pathways

Shah¹,

Thomas²,

Anbalagan³

et al. 2008

Endocrine Related Cancer

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Expression of calcitonin (CT) and its receptor (CTR) is elevated in advanced prostate cancer (PC).Although the significance of CT-CTR axis in PC cell growth, invasion, and epithelial to mesenchymal transition has been established, its role in tumor metastasis has not been examined. To examine the role of CT-CTR axis in tumor metastasis, we employed stable CT-CTR activated and silenced system of three PC cell lines, LNCaP cells that lack endogenous CT, PC-3 cells that lack endogenous CTR, and PC-3M cells that co-express CT and CTR. Enforced expression of CT in LNCaP cells and CTR in PC-3 cells increased their ability to form orthotopic tumors and distant metastases in multiple organs. By contrast, silencing of CT expression in PC-3M cells not only reduced their tumorigenicity, but also completely abrogated their metastatic potential. To investigate the effect of in vivo silencing of CT expression on tumor growth, we employed recombinant adeno-associated virus (rAAV) to deliver anti-CT ribozymes in preexisting tumors of nude mice and large probasin promoter (LPB)-Tag transgenic mice. rAAV-CT K treatment not only abrogated the growth of pre-implanted tumors in nude mice, but also significantly reduced the growth of spontaneous tumors in LPB-Tag mice. Analysis of CT upregulated and silenced PC-3M transcriptomes revealed 105 genes affected by the modulation of CT expression. These CT signature genes generated survival, adhesion, pro-inflammatory, and pro-metastatic pathways. Added together, these data indicate a pivotal role for CT-CTR axis in PC metastasis and may serve as a potential therapeutic target for advanced PC.

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Section: Discussionsupporting

confidence: 85%

Calcitonin promotes in vivo metastasis of prostate cancer cells by altering cell signaling, adhesion, and inflammatory pathways

Shah¹,

Thomas²,

Anbalagan³

et al. 2008

Endocrine Related Cancer

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“…Interestingly, IL-1␣ and IL-8 are known to induce KGF and FGF-2 expression in cultured BPH cells [33,34], and IL-8 can directly promote proliferation of BPH cells [35]. A chronic inflammatory response might thus trigger transdifferentiation of resident stromal cells, resulting in a sustained prostate overgrowth through its growth factors, a situation similar to wound healing [36].…”

Section: Inhibition Of Prostate Inflammation By Bxl-628mentioning

confidence: 98%

Inhibition of prostate growth and inflammation by the vitamin D receptor agonist BXL-628 (elocalcitol)

Adorini

Penna

Amuchastegui

et al. 2007

The Journal of Steroid Biochemistry and Molecular Biology

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“…Paracrine secretion of neuropeptides by NE cells possibly functions to enable the glands only to recover from insult, or the proliferative effect of neuropeptides may be gentler in vivo. Interleukin-6 and interferon-␥ are mentioned as candidates for cytokines, which may induce NE differentiation [23,24] .…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Analysis of Neuroendocrine Differentiation in Prostate Cancer

Ishida

Nakamura²,

Shimada³

et al. 2009

Pathobiology

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Objective: To clarify the significance of neuroendocrine differentiation in prostate cancer. Methods: We immunohistochemically examined 96 samples of prostatic cancers obtained from radical prostatectomies using a specific neuroendocrine marker and various neuropeptides, as well as markers for cell proliferation, angiogenesis and androgen-receptor expression. Results: We frequently found neuroendocrine cells in atrophic glands with or without chronic inflammation in nontumorous tissues. Neuroendocrine cells were detected in 36.5% of prostate cancer samples overall, but had no significant correlation to angiogenesis, cell proliferation or biochemical recurrence. However, patients with a high frequency of neuroendocrine cells (9.4%) tended to undergo preoperative hormonal therapy (p = 0.060), which led to their cancers being atrophic with inflammation. The neuroendocrine cells in these patients contained calcitonin-positive cells (p ≤ 0.0001), and calcitonin positivity showed significant association with high Gleason score (p = 0.045) in the group without preoperative therapy. In the group undergoing preoperative therapy, a high prostate-specific antigen titer at first admission correlated to significant biochemical recurrence (p = 0.003). Conclusions: Neuroendocrine cells may be induced under conditions of atrophy with or without chronic inflammation in both noncancerous glands and in cancers, including calcitonin-positive cells. Neither positive neuroendocrine nor positive androgen-receptor status appears predictive for biochemical recurrence.

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Interferon‐γ induces neuroendocrine‐like differentiation of human prostate basal‐epithelial cells

Abstract: IFN-gamma produced locally in the prostate by basal cells and, under proinflammatory conditions, by infiltrating lymphocytes could support NE cell differentiation and play a role in NE differentiation processes of tumor cells in hormone-refractory prostate cancer.

Cited by 19 publications

References 43 publications

Calcitonin promotes in vivo metastasis of prostate cancer cells by altering cell signaling, adhesion, and inflammatory pathways

Calcitonin promotes in vivo metastasis of prostate cancer cells by altering cell signaling, adhesion, and inflammatory pathways

Inhibition of prostate growth and inflammation by the vitamin D receptor agonist BXL-628 (elocalcitol)

Immunohistochemical Analysis of Neuroendocrine Differentiation in Prostate Cancer

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