Cargando…

Dual Role of TNF and LTα in Carcinogenesis as Implicated by Studies in Mice

SIMPLE SUMMARY: Tumor necrosis factor (TNF) and its closely related cytokine, lymphotoxin alpha (LTα), are part of the TNF superfamily and exert their functions via both overlapping and non-redundant signaling pathways. Reported pro- and antitumorigenic effects of TNF and lymphotoxin are often conte...

Descripción completa

Detalles Bibliográficos
Autores principales: Gubernatorova, Ekaterina O., Polinova, Almina I., Petropavlovskiy, Mikhail M., Namakanova, Olga A., Medvedovskaya, Alexandra D., Zvartsev, Ruslan V., Telegin, Georgij B., Drutskaya, Marina S., Nedospasov, Sergei A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068266/
https://www.ncbi.nlm.nih.gov/pubmed/33917839
http://dx.doi.org/10.3390/cancers13081775
_version_ 1783682995763281920
author Gubernatorova, Ekaterina O.
Polinova, Almina I.
Petropavlovskiy, Mikhail M.
Namakanova, Olga A.
Medvedovskaya, Alexandra D.
Zvartsev, Ruslan V.
Telegin, Georgij B.
Drutskaya, Marina S.
Nedospasov, Sergei A.
author_facet Gubernatorova, Ekaterina O.
Polinova, Almina I.
Petropavlovskiy, Mikhail M.
Namakanova, Olga A.
Medvedovskaya, Alexandra D.
Zvartsev, Ruslan V.
Telegin, Georgij B.
Drutskaya, Marina S.
Nedospasov, Sergei A.
author_sort Gubernatorova, Ekaterina O.
collection PubMed
description SIMPLE SUMMARY: Tumor necrosis factor (TNF) and its closely related cytokine, lymphotoxin alpha (LTα), are part of the TNF superfamily and exert their functions via both overlapping and non-redundant signaling pathways. Reported pro- and antitumorigenic effects of TNF and lymphotoxin are often context-dependent and may be contingent on a particular experimental approach, such as transplantable and chemically induced tumor models; tissue and organ specificity; types of cells producing these cytokines or responding to them; and the genotype and genetic background of mice. Here, we review the mechanisms of TNF/LTα involvement in cancer promotion and suppression as studied in mouse models. We also discuss the impact of microbiota on tumor development and manipulations of the TNF/LT system, which may be effective as anti-cancer therapy. ABSTRACT: Tumor necrosis factor (TNF) and lymphotoxin alpha (LTα) are two related cytokines from the TNF superfamily, yet they mediate their functions in soluble and membrane-bound forms via overlapping, as well as distinct, molecular pathways. Their genes are encoded within the major histocompatibility complex class III cluster in close proximity to each other. TNF is involved in host defense, maintenance of lymphoid tissues, regulation of cell death and survival, and antiviral and antibacterial responses. LTα, known for some time as TNFβ, has pleiotropic functions including control of lymphoid tissue development and homeostasis cross talk between lymphocytes and their environment, as well as lymphoid tissue neogenesis with formation of lymphoid follicles outside the lymph nodes. Along with their homeostatic functions, deregulation of these two cytokines may be associated with initiation and progression of chronic inflammation, autoimmunity, and tumorigenesis. In this review, we summarize the current state of knowledge concerning TNF/LTα functions in tumor promotion and suppression, with the focus on the recently uncovered significance of host–microbiota interplay in cancer development that may explain some earlier controversial results.
format Online
Article
Text
id pubmed-8068266
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80682662021-04-25 Dual Role of TNF and LTα in Carcinogenesis as Implicated by Studies in Mice Gubernatorova, Ekaterina O. Polinova, Almina I. Petropavlovskiy, Mikhail M. Namakanova, Olga A. Medvedovskaya, Alexandra D. Zvartsev, Ruslan V. Telegin, Georgij B. Drutskaya, Marina S. Nedospasov, Sergei A. Cancers (Basel) Review SIMPLE SUMMARY: Tumor necrosis factor (TNF) and its closely related cytokine, lymphotoxin alpha (LTα), are part of the TNF superfamily and exert their functions via both overlapping and non-redundant signaling pathways. Reported pro- and antitumorigenic effects of TNF and lymphotoxin are often context-dependent and may be contingent on a particular experimental approach, such as transplantable and chemically induced tumor models; tissue and organ specificity; types of cells producing these cytokines or responding to them; and the genotype and genetic background of mice. Here, we review the mechanisms of TNF/LTα involvement in cancer promotion and suppression as studied in mouse models. We also discuss the impact of microbiota on tumor development and manipulations of the TNF/LT system, which may be effective as anti-cancer therapy. ABSTRACT: Tumor necrosis factor (TNF) and lymphotoxin alpha (LTα) are two related cytokines from the TNF superfamily, yet they mediate their functions in soluble and membrane-bound forms via overlapping, as well as distinct, molecular pathways. Their genes are encoded within the major histocompatibility complex class III cluster in close proximity to each other. TNF is involved in host defense, maintenance of lymphoid tissues, regulation of cell death and survival, and antiviral and antibacterial responses. LTα, known for some time as TNFβ, has pleiotropic functions including control of lymphoid tissue development and homeostasis cross talk between lymphocytes and their environment, as well as lymphoid tissue neogenesis with formation of lymphoid follicles outside the lymph nodes. Along with their homeostatic functions, deregulation of these two cytokines may be associated with initiation and progression of chronic inflammation, autoimmunity, and tumorigenesis. In this review, we summarize the current state of knowledge concerning TNF/LTα functions in tumor promotion and suppression, with the focus on the recently uncovered significance of host–microbiota interplay in cancer development that may explain some earlier controversial results. MDPI 2021-04-08 /pmc/articles/PMC8068266/ /pubmed/33917839 http://dx.doi.org/10.3390/cancers13081775 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Gubernatorova, Ekaterina O.
Polinova, Almina I.
Petropavlovskiy, Mikhail M.
Namakanova, Olga A.
Medvedovskaya, Alexandra D.
Zvartsev, Ruslan V.
Telegin, Georgij B.
Drutskaya, Marina S.
Nedospasov, Sergei A.
Dual Role of TNF and LTα in Carcinogenesis as Implicated by Studies in Mice
title Dual Role of TNF and LTα in Carcinogenesis as Implicated by Studies in Mice
title_full Dual Role of TNF and LTα in Carcinogenesis as Implicated by Studies in Mice
title_fullStr Dual Role of TNF and LTα in Carcinogenesis as Implicated by Studies in Mice
title_full_unstemmed Dual Role of TNF and LTα in Carcinogenesis as Implicated by Studies in Mice
title_short Dual Role of TNF and LTα in Carcinogenesis as Implicated by Studies in Mice
title_sort dual role of tnf and ltα in carcinogenesis as implicated by studies in mice
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068266/
https://www.ncbi.nlm.nih.gov/pubmed/33917839
http://dx.doi.org/10.3390/cancers13081775
work_keys_str_mv AT gubernatorovaekaterinao dualroleoftnfandltaincarcinogenesisasimplicatedbystudiesinmice
AT polinovaalminai dualroleoftnfandltaincarcinogenesisasimplicatedbystudiesinmice
AT petropavlovskiymikhailm dualroleoftnfandltaincarcinogenesisasimplicatedbystudiesinmice
AT namakanovaolgaa dualroleoftnfandltaincarcinogenesisasimplicatedbystudiesinmice
AT medvedovskayaalexandrad dualroleoftnfandltaincarcinogenesisasimplicatedbystudiesinmice
AT zvartsevruslanv dualroleoftnfandltaincarcinogenesisasimplicatedbystudiesinmice
AT telegingeorgijb dualroleoftnfandltaincarcinogenesisasimplicatedbystudiesinmice
AT drutskayamarinas dualroleoftnfandltaincarcinogenesisasimplicatedbystudiesinmice
AT nedospasovsergeia dualroleoftnfandltaincarcinogenesisasimplicatedbystudiesinmice