2018
DOI: 10.3390/ijms19041223
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Bone Cell Activity in Clinical Prostate Cancer Bone Metastasis and Its Inverse Relation to Tumor Cell Androgen Receptor Activity

Abstract: Advanced prostate cancer frequently metastasizes to bone and induces a mixed osteoblastic/osteolytic bone response. Standard treatment for metastatic prostate cancer is androgen-deprivation therapy (ADT) that also affects bone biology. Treatment options for patients relapsing after ADT are limited, particularly in cases where castration-resistance does not depend on androgen receptor (AR) activity. Patients with non-AR driven metastases may, however, benefit from therapies targeting the tumor microenvironment.… Show more

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Cited by 29 publications
(21 citation statements)
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“…Moreover, a high co-expression of Smad7 and HDAC6, and c-Jun and HDAC6, was observed in prostate cancer tissues, which correlated with poor prognosis ( Figure 9D). We have recently reported that both TbRI and c-Jun are expressed at high levels in aggressive prostate cancer tissues (Gudey et al, 2017), and high levels of Smad7 have been reported to be expressed in prostate cancer bone metastases (Nordstrand et al, 2018), providing support for the notion that active TGF-b signaling promotes prostate cancer progression and metastases, in line with our observations in this report.…”
Section: Open Accesssupporting
confidence: 89%
“…Moreover, a high co-expression of Smad7 and HDAC6, and c-Jun and HDAC6, was observed in prostate cancer tissues, which correlated with poor prognosis ( Figure 9D). We have recently reported that both TbRI and c-Jun are expressed at high levels in aggressive prostate cancer tissues (Gudey et al, 2017), and high levels of Smad7 have been reported to be expressed in prostate cancer bone metastases (Nordstrand et al, 2018), providing support for the notion that active TGF-b signaling promotes prostate cancer progression and metastases, in line with our observations in this report.…”
Section: Open Accesssupporting
confidence: 89%
“…The less common and poorly defined subgroup MetC is identified based on enrichment of transcripts involved in stroma–epithelial interactions such as cell adhesion, cell and tissue remodeling, immune responses, and inflammation. Processes in MetC thus resemble those previously described by us for non‐AR‐driven bone metastases (Nordstrand et al ., ; Ylitalo et al ., ). One suggested upstream regulator of MetC is the C/EBP transcription factor, generally associated with inflammation and downregulated by AR signaling (Barakat et al ., ).…”
Section: Discussionmentioning
confidence: 97%
“…By exploring the transcriptome and proteome of bone metastases from patients, we have identified marked differences between metastases and primary tumors and, furthermore, identified bone metastasis subgroups of apparent biological importance (Djusberg et al, 2017;H€ ornberg et al, 2011;Iglesias-Gato et al, 2018;Jernberg et al, 2013;Nordstrand et al, 2018;Ylitalo et al, 2017). Based on gene expression of canonically androgen receptor (AR) regulated genes, 80% of the examined PC bone metastases were defined as AR-driven and 20% were defined as non-AR-driven (Ylitalo et al, 2017).…”
Section: Introductionmentioning
confidence: 99%
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“…Meanwhile, destruction of bone tissue leads to aberrant release of a multitude of bone-derived growth factors, which further stimulate migration and proliferation of tumor cells. 10 Based on the primary mechanism of bone remodeling disturbance, bone metastasis can be predominantly classified into three categories: osteolytic, osteoblastic or mixed. In general, osteolytic lesions are most commonly observed in patients with breast cancer and multiple myeloma, 1,11 while the most common skeletal complication of prostate cancer tend to be osteoblastic rather than osteolytic.…”
Section: Discussionmentioning
confidence: 99%