Advanced prostate cancer: reinforcing the strings between inflammation and the metastatic behavior

Gueron, Geraldine; Siervi, Adriana De; Vázquez, Elba S.

doi:10.1038/pcan.2011.64

Cited by 49 publications

(41 citation statements)

References 116 publications

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“…This inflammatory scenario creates a reactive microenvironment that fosters detachment, migration and invasion of malignant cells. In this context, we previously documented the critical role of HO-1, an anti-inflammatory and anti-oxidant protein in impairing tumor growth, inhibiting cell invasion and migration in PCa [13, 20, 37, 38]. The role of HO-1 in cancer still remains a controversial subject.…”

Section: Discussionmentioning

confidence: 99%

Heme-oxygenase-1 implications in cell morphology and the adhesive behavior of prostate cancer cells

et al. 2014

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Prostate cancer (PCa) is the second leading cause of cancer death in men. Although previous studies in PCa have focused on cell adherens junctions (AJs), key players in metastasis, they have left the molecular mechanisms unexplored. Inflammation and the involvement of reactive oxygen species (ROS) are critical in the regulation of cell adhesion and the integrity of the epithelium. Heme oxygenase-1 (HO-1) counteracts oxidative and inflammatory damage. Here, we investigated whether HO-1 is implicated in the adhesive and morphological properties of tumor cells. Genes differentially regulated by HO-1 were enriched for cell motility and adhesion biological processes. HO-1 induction, increased E-cadherin and β-catenin levels. Immunofluorescence analyses showed a striking remodeling of E-cadherin/β-catenin based AJs under HO-1 modulation. Interestingly, the enhanced levels of E-cadherin and β-catenin coincided with a markedly change in cell morphology. To further our analysis we sought to identify HO-1 binding proteins that might participate in the regulation of cell morphology. A proteomics approach identified Muskelin, as a novel HO-1 partner, strongly implicated in cell morphology regulation. These results define a novel role for HO-1 in modulating the architecture of cell-cell interactions, favoring a less aggressive phenotype and further supporting its anti-tumoral function in PCa.

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Section: Discussionmentioning

confidence: 99%

Heme-oxygenase-1 implications in cell morphology and the adhesive behavior of prostate cancer cells

et al. 2014

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“…Both HIF2α and HIF3α appear expressed in a cell-specific manner and play non redundant roles in adapting to hypoxia and in hypoxic tumor growth and progression [14], [15]. Increasing evidence indicates that the inflammatory microenvironment is a further contributing factor leading to cancer development in the prostate [16], [17]. Inflammatory gene response depends on several transcription factors, among which NF-kB plays a central role.…”

Section: Introductionmentioning

confidence: 99%

Distinct Phenotypes of Human Prostate Cancer Cells Associate with Different Adaptation to Hypoxia and Pro-Inflammatory Gene Expression

Ravenna

Principessa

Verdina³

et al. 2014

PLoS ONE

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Hypoxia and inflammation are strictly interconnected both concurring to prostate cancer progression. Numerous reports highlight the role of tumor cells in the synthesis of pro-inflammatory molecules and show that hypoxia can modulate a number of these genes contributing substantially to the increase of cancer aggressiveness. However, little is known about the importance of the tumor phenotype in this process. The present study explores how different features, including differentiation and aggressiveness, of prostate tumor cell lines impact on the hypoxic remodeling of pro-inflammatory gene expression and malignancy. We performed our studies on three cell lines with increasing metastatic potential: the well differentiated androgen-dependent LNCaP and the less differentiated and androgen-independent DU145 and PC3. We analyzed the effect that hypoxic treatment has on modulating pro-inflammatory gene expression and evaluated the role HIF isoforms and NF-kB play in sustaining this process. DU145 and PC3 cells evidenced a higher normoxic expression and a more complete hypoxic induction of pro-inflammatory molecules compared to the well differentiated LNCaP cell line. The role of HIF1α and NF-kB, the master regulators of hypoxia and inflammation respectively, in sustaining the hypoxic pro-inflammatory phenotype was different according to cell type. NF-kB was observed to play a main role in DU145 and PC3 cells in which treatment with the NF-kB inhibitor parthenolide was able to counteract both the hypoxic pro-inflammatory shift and HIF1α activation but not in LNCaP cells. Our data highlight that tumor prostate cell phenotype contributes at a different degree and with different mechanisms to the hypoxic pro-inflammatory gene expression related to tumor progression.

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“…Although neuroendocrine differentiation is rare in early PC, most drug-resistant and aggressive forms of PC exhibit a neuroendocrine phenotype (3)(4)(5). Treatment options for CRPC are limited, mostly because of intrinsic chemoresistance and the increased metastatic potential acquired by PC cells during disease progression (6). Identifying new targets for the prevention or treatment of CRPC and drugresistant neuroendocrine PC is therefore of great importance.…”

mentioning

confidence: 99%

Tissue injury and hypoxia promote malignant progression of prostate cancer by inducing CXCL13 expression in tumor myofibroblasts

Ammirante

Shalapour

Kang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

172

124

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Prostate cancer (PC) is a slowly progressing malignancy that often responds to androgen ablation or chemotherapy by becoming more aggressive, acquiring a neuroendocrine phenotype, and undergoing metastatic spread. We found that B lymphocytes recruited into regressing androgen-deprived tumors by C-X-C motif chemokine 13 (CXCL13), a chemokine whose expression correlates with clinical severity, play an important role in malignant progression and metastatic dissemination of PC. We now describe how androgen ablation induces CXCL13 expression. In both allografted and spontaneous mouse PC, CXCL13 is expressed by tumor-associated myofibroblasts that are activated on androgen ablation through a hypoxia-dependent mechanism. The same cells produce CXCL13 after chemotherapy. Myofibroblast activation and CXCL13 expression also occur in the normal prostate after androgen deprivation, and CXCL13 is expressed by myofibroblasts in human PC. Hypoxia activates hypoxia-inducible factor 1 (HIF-1) and induces autocrine TGF-β signaling that promotes myofibroblast activation and CXCL13 induction. In addition to TGF-β receptor kinase inhibitors, myofibroblast activation and CXCL13 induction are blocked by phosphodiesterase 5 (PDE5) inhibitors. Both inhibitor types and myofibroblast immunodepletion block the emergence of castration-resistant PC in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of spontaneous metastatic PC with neuroendocrine differentiation.tumor microenvironment | inflammation | cancer | cancer-associated fibroblasts

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Advanced prostate cancer: reinforcing the strings between inflammation and the metastatic behavior

Cited by 49 publications

References 116 publications

Heme-oxygenase-1 implications in cell morphology and the adhesive behavior of prostate cancer cells

Heme-oxygenase-1 implications in cell morphology and the adhesive behavior of prostate cancer cells

Distinct Phenotypes of Human Prostate Cancer Cells Associate with Different Adaptation to Hypoxia and Pro-Inflammatory Gene Expression

Tissue injury and hypoxia promote malignant progression of prostate cancer by inducing CXCL13 expression in tumor myofibroblasts

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