Secreted Factors from Colorectal and Prostate Cancer Cells Skew the Immune Response in Opposite Directions

Lundholm, Marie; Hägglöf, Christina; Wikberg, Maria L.; Stattin, Pär; Egevad, Lars; Bergh, Anders; Wikström, Pernilla; Palmqvist, Richard; Edin, Sofia

doi:10.1038/srep15651

Cited by 79 publications

(94 citation statements)

References 40 publications

(59 reference statements)

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“…In TINT, the proportion of C/EBP‐beta + epithelial cells was inversely correlated to tumor size (Rs = −0.18, n = 338, P < 0.01) and Gleason score (Rs = −0.15, n = 338, P < 0.01), and was positively correlated to the density of iNOS + (M1‐type) macrophages (Rs = 0.16, n = 187, P = 0.028; data from ), but not to the density of other types of inflammatory cells such as mast cells and CD163 + (M2‐type) macrophages in TINT.…”

Section: Resultsmentioning

confidence: 98%

“…Mediators of inflammation such as interleukin‐1 (IL‐1), IL‐6, TNF‐alpha, and LPS all increases C/EBPβ expression . Prostate cancer is associated with accumulation of subsets of inflammatory cells within the tumor and outside in the TINT, and IL1, IL6, and TNF‐alpha are upregulated in the prostate tumor microenvironment . It is therefore likely that tumor‐induced inflammation contributed to increase epithelial C/EBPβ expression within and outside the tumor.…”

Section: Discussionmentioning

confidence: 99%

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Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome

et al. 2018

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Background Implantation of rat prostate cancer cells into the normal rat prostate results in tumor‐stimulating adaptations in the tumor‐bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non‐malignant part of tumor‐bearing prostate lobe in rats was the transcription factor CCAAT/enhancer‐binding protein‐β (C/EBPβ). Methods To explore this further, we examined C/EBPβ expression by quantitative RT‐PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow‐growing non‐metastatic Dunning G, rapidly growing poorly metastatic (AT‐1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors―and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting. Results In rats, C/EBPβ mRNA expression was upregulated in the surrounding tumor‐bearing prostate lobe. In tumors and in the surrounding non‐malignant prostate tissue, C/EBPβ was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBPβ expression in the tumor‐bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBPβ in glandular epithelial cells in the surrounding tumor‐bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBPβ in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome. Conclusions This study suggest that the expression of C/EBP‐beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor‐bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome

et al. 2018

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“…Furthermore, we have shown that the majority of infiltrating macrophages in prostate cancer patients have an M2 phenotype and are associated with poor patient prognosis51. We therefore examined if tumor-EVs had the capacity to attract macrophages to the normal prostate tissue.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles from Metastatic Rat Prostate Tumors Prime the Normal Prostate Tissue to Facilitate Tumor Growth

Bergström

Hägglöf

Thysell

et al. 2016

Sci Rep

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Accumulating data indicates that tumor-derived extracellular vesicles (EVs) are responsible for tumor-promoting effects. However, if tumor EVs also prepare the tumor-bearing organ for subsequent tumor growth, and if this effect is different in low and high malignant tumors is not thoroughly explored. Here we used orthotopic rat Dunning R-3327 prostate tumors to compare the role of EVs from fast growing and metastatic MatLyLu (MLL) tumors with EVs from more indolent and non-metastatic Dunning G (G) tumors. Prostate tissue pre-conditioned with MLL-EVs in vivo facilitated G tumor establishment compared to G-EVs. MLL-EVs increased prostate epithelial proliferation and macrophage infiltration into the prostate compared to G-EVs. Both types of EVs increased macrophage endocytosis and the mRNA expression of genes associated with M2 polarization in vitro, with MLL-EVs giving the most pronounced effects. MLL-EVs also altered the mRNA expression of growth factors and cytokines in primary rat prostate fibroblasts compared to G-EVs, suggesting fibroblast activation. Our findings propose that EVs from metastatic tumors have the ability to prime the prostate tissue and enhance tumor growth to a higher extent than EVs from non-metastatic tumors. Identifying these differences could lead to novel therapeutic targets and potential prognostic markers for prostate cancer.

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“…C . Increased levels of the macrophage-associated scavenger receptor CD163 have been found in affected tissues of patients with MS265, AD266, PD266, AS267, and cancer (breast268, prostate269, glioblastoma270. D .…”

Section: Iron Oxide Nanoparticlesmentioning

confidence: 99%

Targeting iron metabolism in drug discovery and delivery

Crielaard

Lammers

Rivella

2017

Nat Rev Drug Discov

280

205

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Iron fulfils a central role in many essential biochemical processes in human physiology, which makes proper processing of iron crucial. Although iron metabolism is subject to relatively strict physiological control, in recent years numerous disorders, such as cancer and neurodegenerative diseases, have been linked to deregulated iron homeostasis. Because of its involvement in the pathogenesis of these diseases, iron metabolism constitutes a promising and largely unexploited therapeutic target for the development of new pharmacological treatments. Several iron metabolism-targeted therapies are already under clinical evaluation for haematological disorders, and these and newly developed therapeutic agents will likely have substantial benefit in the clinical management of iron metabolism-associated diseases, for which few efficacious treatments are often available.

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Secreted Factors from Colorectal and Prostate Cancer Cells Skew the Immune Response in Opposite Directions

Cited by 79 publications

References 40 publications

Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome

Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome

Extracellular Vesicles from Metastatic Rat Prostate Tumors Prime the Normal Prostate Tissue to Facilitate Tumor Growth

Targeting iron metabolism in drug discovery and delivery

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