Lymphotoxin’s Link to Carcinogenesis: Friend or Foe? From Lymphoid Neogenesis to Hepatocellular Carcinoma and Prostate Cancer

Wolf, Monika; Seleznik, Gitta Maria; Heikenwälder, Mathias

doi:10.1007/978-1-4419-6612-4_24

Cited by 5 publications

(5 citation statements)

References 96 publications

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“…e-h ). This suggests that Lymphotoxin β receptor (LTβR) activation by LTα, LTβ and/or LIGHT could play a key role in ELS assembly and pro-tumorigenic processes 26 , 27 , 28 , 29 . LTβR was reported to be expressed on hepatocytes, whereas LTα and LTβ are normally expressed in lymphocytes 30 .…”

Section: Resultsmentioning

confidence: 99%

Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma

et al. 2015

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Ectopic lymphoid-like structures (ELS) are often observed in cancer, yet their function is obscure. Although ELSs signify good prognosis in certain malignancies, we found that hepatic ELSs indicate poor prognosis in hepatocellular carcinoma (HCC). We studied an HCC mouse model, displaying abundant ELSs and found that they constitute immunopathological microniches, wherein progenitor malignant hepatocytes appear and thrive in a complex cellular and cytokine milieu until gaining self-sufficiency. Progenitor egression and tumor formation is associated with autocrine production of cytokines previously provided by the niche. ELSs develop upon cooperation between the innate and adaptive immune system which is facilitated by NF-κB activation and abolished by T cell depletion. These aberrant immune foci could be new targets for cancer therapy.

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Section: Resultsmentioning

confidence: 99%

Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma

et al. 2015

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“…Although immense progress has been made in the past to understand the mechanism(s) by which chronic inflammation influences tissue integrity, chromosomal stability, apoptosis, proliferation and cancer development, the exact pathways and cellular ingredients that define inflammation as anti-or pro-carcinogenic remain unknown. The initial composition of immune cells in the target organ, the cells infiltrating or surrounding tumour tissue, the interaction of the tumour stroma with immune cells, the expression of cytokines and chemokines and the organ in which chronic inflammation occurs might explain why inflammation is a double-edged sword [15,19,29,35]. Furthermore, it remains elusive if the transition from chronic inflammation to cancer underlies specific pathways or if the existence of an inflammatory environment unspecifically increases the stochastic likelihood to cause cancer.…”

Section: Chronic Inflammation -A State Which Fosters Multiple Hallmar...mentioning

confidence: 99%

“…We recently showed that LTα, β and their receptor (LTbR) are increased in intrahepatic lymphocytes and hepatocytes of patients with HBV-or HCV-induced chronic hepatitis or HCC [53]. Various other liver diseases of non-viral aeti-ology have shown significantly lower levels of LTα, β and LTβR mRNA expression [35,53]. Thus, the question remained whether LT expression in mice suffices to induce liver inflammation and HCC.…”

Section: The Albltαβ Mouse Modelmentioning

confidence: 99%

Chronic liver inflammation and hepatocellular carcinoma: persistence matters

Weber¹,

Boege²,

Reisinger³

et al. 2011

Swiss Med Wkly

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Inflammatory responses in the liver--a central constituent of hepatic wound healing--can be self-limited or persistent depending on the aetiology, liver health state, concentration of toxins or pathogens, and the time frame of exposure to toxins or infection. In case the immune system eradicates a pathogen or in case toxin-exposure is transient, acute hepatitis resolves and the affected liver tissue regenerates ad integrum. However, in many cases liver damage remains chronic. Irrespective of the aetiology, chronic liver damage drives chronic hepatitis and hepatocyte death as well as compensatory proliferation, reflecting liver regeneration. Over time this potentially promotes further hepatic damage, fibrosis, cirrhosis and liver cancer. Here, we review the current knowledge on how chronic liver injury and inflammation is triggered and maintained, and how inflammation is linked to liver cancer. We also discuss the most frequently used animal models for damage or inflammation induced liver cancer and their suitability for conducting clinically relevant research.

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“…Consistently, AlbLTαβ mice that lack B and T cells (AlbLTαβ Rag1 ‐/‐ ) fail to develop chronic hepatitis and HCC (Haybaeck et al., ). These findings indicate that the role of NF‐κB signaling in liver cancer development might depend on the model, the time frame, and the type or degree of liver inflammation and injury (Vainer et al., ; Grivennikov et al., ; Wolf et al., ).…”

Section: Mouse Genetic Models Mimicking Chronic Inflammation and Chromentioning

confidence: 99%

“…It is established that IKKβ signaling is important for hepatocytes to respond to and survive acute liver injury and DEN exposure (Maeda et al, 2005). In its absence, the amount of damaged and proliferating hepatocytes is increased, enhancing the potential for the (Vainer et al, 2008;Grivennikov et al, 2010;Wolf et al, 2011).…”

Section: Albltαβ Mouse Modelmentioning

confidence: 99%

Modeling Human Liver Cancer Heterogeneity: Virally Induced Transgenic Models and Mouse Genetic Models of Chronic Liver Inflammation

Ringelhan

Reisinger²,

Yuan³

et al. 2014

CP Pharmacology

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In addition to being the most common primary liver cancer, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in humans. Treatment options are limited for this chemoresistant cancer, with liver transplantation and surgical intervention in early stages being the most successful treatments. Drug development over the past 15 years has focused on generating mouse models that mimic the human pathology for HCC. This has enabled the laboratory testing of potentially new human therapeutics. Described in this unit are the classification of HCC and an overview of hepatitis virus-related transgenic and genetically engineered mouse models (GEMMs) that are employed for elucidating the mechanism(s) responsible for the development of HCC, with particular emphasis on genetic, dietary, and environmental factors.

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Lymphotoxin’s Link to Carcinogenesis: Friend or Foe? From Lymphoid Neogenesis to Hepatocellular Carcinoma and Prostate Cancer

Cited by 5 publications

References 96 publications

Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma

Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma

Chronic liver inflammation and hepatocellular carcinoma: persistence matters

Modeling Human Liver Cancer Heterogeneity: Virally Induced Transgenic Models and Mouse Genetic Models of Chronic Liver Inflammation

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