The expression of osteoclastogenesis‐associated factors and osteoblast response to osteolytic prostate cancer cells

Morrissey, Colm; Lai, Janice S.; Brown, Lisha G.; Wang, Ya Chun; Roudier, Martine P.; Coleman, Ilsa M.; Gulati, Roman; Vakar-López, Funda; True, Lawrence D.; Corey, Eva; Nelson, Peter S.; Vessella, Robert L.

doi:10.1002/pros.21075

Cited by 40 publications

(35 citation statements)

References 25 publications

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“…These analyses indicated that under identical conditions, the newer version of the antibody does not stain tumor cells in bone metastases, yet, the older antibody batch gave similar results to that reported previously (15) with strong tumor cell staining (C. Morrissey, unpublished data). Taken together with the present study, it would appear that prior results showing high level expression in tumor cells is related to antibody lot variability and it no longer appears with the newer currently available antibody from the same vendor.…”

Section: Discussionsupporting

confidence: 80%

“…Likewise, a previous study using IHC to detect IL6 production in prostate cancer metastases reported over twice as many bone metastases samples are positive for IL6 than soft tissue metastases, and with much stronger staining intensity (15). Unfortunately, our data do not support those results.…”

Section: Discussionmentioning

confidence: 92%

“…Previous studies suggested that production of IL6 by metastatic prostate cancer cells may facilitate invasion and metastasis to bone and/or promote resistance to prostate cancer therapies (15, 22). Therefore, we next examined IL6 mRNA expression in biopsy samples from patients with castration-resistant metastatic prostate cancer (samples evaluated included 4 lymph node specimens and 3 liver biopsy samples) and 25 autopsy samples which included metastases to the liver, lung, bone, and lymph node (see Supplementary Table S1).…”

Section: Resultsmentioning

confidence: 99%

“…To help determine whether we could account for the discrepant results between a past study (15) and the present one, we compared by IHC the staining obtained with the polyclonal anti-IL6 antibody batch (#6672; Abcam, lot # 385304) that was used previously to the currently commercially available batch (lot # GR169214-2). These analyses indicated that under identical conditions, the newer version of the antibody does not stain tumor cells in bone metastases, yet, the older antibody batch gave similar results to that reported previously (15) with strong tumor cell staining (C. Morrissey, unpublished data).…”

Section: Discussionmentioning

confidence: 98%

“…Furthermore, studies using immunohistochemistry (IHC) to detect IL6 in prostate tissues have reported IL6 production by both benign and malignant prostate epithelium (13, 14). An additional study utilizing IHC to detect IL6 in a series of metastatic tissues from 26 prostate cancer patients reported that IL6 is produced in the majority of prostate cancer bone metastases and to a lesser extent in prostate cancer soft tissue metastases (15). Another series of studies proposed that IL6 along with a related member of the IL6 family of cytokines, oncostatin M (OSM), may activate androgen receptor (AR) in the absence of androgen, providing a potential mechanism whereby IL-6 contributes to recurrent prostate cancer growth following androgen deprivation therapy (reviewed in (16)).…”

Section: Introductionmentioning

confidence: 99%

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A Paracrine Role for IL6 in Prostate Cancer Patients: Lack of Production by Primary or Metastatic Tumor Cells

Zheng

Esopi

et al. 2015

Cancer Immunology Research

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Correlative human studies suggest that the pleiotropic cytokine interleukin-6 (IL6) contributes to the development and/or progression of prostate cancer. However, the source of IL6 production in the prostate microenvironment in patients has yet to be determined. The cellular origin of IL6 in primary and metastatic prostate cancer was examined in formalin-fixed, paraffin-embedded (FFPE) tissues using a highly sensitive and specific chromogenic in situ hybridization (CISH) assay that underwent extensive analytical validation. Quantitative RT-PCR (q-RT-PCR) showed that benign prostate tissues often had higher expression of IL6 mRNA than matched tumor specimens. CISH analysis further indicated that both primary and metastatic prostate adenocarcinoma cells do not express IL6 mRNA. IL6 expression was highly heterogeneous across specimens and was nearly exclusively restricted to the prostate stromal compartment – including endothelial cells and macrophages among other cell types. The number of IL6-expressing cells correlated positively with the presence of acute inflammation. In metastatic disease, tumor cells were negative in all lesions examined and IL6 expression was restricted to endothelial cells within the vasculature of bone metastases. Finally, IL6 was not detected in any cells in soft tissue metastases. These data suggest that, in prostate cancer patients, paracrine rather than autocrine IL6 production is likely associated with any role for the cytokine in disease progression.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A Paracrine Role for IL6 in Prostate Cancer Patients: Lack of Production by Primary or Metastatic Tumor Cells

Zheng

Esopi

et al. 2015

Cancer Immunology Research

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MicroRNA-199a/b-3p: A new star in the liver microcosmos

Roderburg

Luedde

2011

Hepatology

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The full scale of human miRNome in specific cell or tissue, especially in cancers, remains to be determined. An in-depth analysis of miRNomes in human normal liver, hepatitis liver, and hepatocellular carcinoma (HCC) was carried out in this study. We found nine miRNAs accounted for 88.2% of the miRNome in human liver. The third most highly expressed miR-199a/b-3p is consistently decreased in HCC, and its decrement significantly correlates with poor survival of HCC patients. Moreover, miR-199a/b-3p can target tumorpromoting PAK4 to suppress HCC growth through inhibiting PAK4/Raf/ MEK/ERK pathway both in vitro and in vivo. Our study provides miRNomes of human liver and HCC and contributes to better understanding of the important deregulated miRNAs in HCC and liver diseases. CommentMicroRNAs (miRNAs) are small RNAs of 22 nucleotides length that do not hold the sequential information to transcribe proteins, but function as critical regulators of gene expression in multicellular and some unicellular eukaryotes.1 Pre-miRNAs undergo sequential processing by the ribonuclease III endonucleases Drosha and Dicer, leading to the mature 20-to 23-nucleotide species.2 These in turn are integrated into the RNA-induced silencing complex (RISC) and recognize their target genes by interacting with complementary sequences in the 3 0 untranslated region of their messenger RNAs (mRNAs). In the case of perfect or nearly perfect pairing, the target mRNA becomes degraded, whereas imperfect pairing leads to translational repression of the latter.3 Importantly, an individual miRNA can regulate hundreds of transcripts and thus can coordinate complex networks of gene expression and subsequently induce global changes in cellular physiology and pathophysiology. Indeed, in addition to genetic and epigenetic abnormalities modifying oncogenes and tumor suppressor genes, deregulation of miRNAs has been shown to contribute to carcinogenesis of both solid and hematological malignancy. 4,5 In recent years, significant efforts were taken to identify miRNAs that regulate hepatocarcinogenesis. Altered expression patterns of miRNAs have been described in both rodent and human hepatocellular carcinoma (HCC) in studies using microarray technology or quantitative polymerase chain reaction (qPCR). In 2006, Murakami et al. reported on a panel of eight miRNAs that were significantly altered in HCC, comprising the miR-199 family, which was also down-regulated in their collective. 6 In the following years, a whole kaleidoscope of other deregulated miRNAs were reported by different groups in the context of HCC.7 Furthermore, specific targets were linked to miRNAs deregulated in HCC, including genes involved in tumor metastasis such as focal adhesion kinase (targeted by miR-151), 8,9 cellcycle-modulating proteins such as cyclin G1 (targeted by miR-122), 10 or the cyclin-dependent kinase inhibitors CDKN1B/p27 and CDKN1C/p57 (targeted by miR-221).11 However, as the authors of the present article point out, the results obtained from these previous microar...

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Gefitinib inhibits the cross‐talk between mesenchymal stem cells and prostate cancer cells leading to tumor cell proliferation and inhibition of docetaxel activity

Borghese

Cattaruzza

Pivetta

et al. 2013

J of Cellular Biochemistry

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Increasing evidence suggests that bone marrow derived mesenchymal stem cells (BM-MSCs) are recruited into the stroma of developing tumors where they contribute to progression by enhancing tumor growth and metastasis, or by inducing anticancer-drug resistance. Prostate cancer cells secrete ligands of epidermal growth factor receptor (EGFR) and EGFR signaling could play an important role in the cross-talk between mesenchymal stem cells and prostate cancer cells. In this study, we showed that treatment of human primary MSCs with conditioned medium (CM) derived from the bone metastatic PC3 carcinoma cells (PC3-CM) resulted in: a significant activation of EGFR; increased proliferation; increased osteoblastic but decreased adipocitic differentiation; inhibition of senescence induced by serum starvation; increased CCL5 secretion. These activities were significantly inhibited in the presence of the EGFR tyrosine kinase inhibitor gefitinib. PC3-CM directly inhibited osteoclastogenesis as well as the ability of osteoblasts to induce osteoclast differentiation. The increased MSCs migration by PC3-CM and PC3 cells was partially mediated by CCL5. MSC-CM increased the formation of colonies by PC3 cells and inhibited the anti-proliferative activity of Docetaxel. Activation of EGFR expressed on MSCs by PC3-CM enhanced their capability to increase PC3 cells proliferation and to inhibit Docetaxel activity. These findings, by showing that the tumor-promoting interactions between PC3 cells and MSCs are mediated, at least in part, by EGFR, suggest a novel application of the EGFR-tyrosine kinase inhibitors in the treatment of prostate cancer.

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The expression of osteoclastogenesis‐associated factors and osteoblast response to osteolytic prostate cancer cells

Cited by 40 publications

References 25 publications

A Paracrine Role for IL6 in Prostate Cancer Patients: Lack of Production by Primary or Metastatic Tumor Cells

A Paracrine Role for IL6 in Prostate Cancer Patients: Lack of Production by Primary or Metastatic Tumor Cells

MicroRNA-199a/b-3p: A new star in the liver microcosmos

Gefitinib inhibits the cross‐talk between mesenchymal stem cells and prostate cancer cells leading to tumor cell proliferation and inhibition of docetaxel activity

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