Chronic inflammation promotes cancer progression by affecting the tumor cells and their microenvironment. Here, we demonstrate that a continuous stimulation (~6 weeks) of triple-negative breast tumor cells (TNBC) by the proinflammatory cytokines tumor necrosis factor α (TNFα) + interleukin 1β (IL-1β) changed the expression of hundreds of genes, skewing the cells towards a proinflammatory phenotype. While not affecting stemness, the continuous TNFα + IL-1β stimulation has increased tumor cell dispersion and has induced a hybrid metabolic phenotype in TNBC cells; this phenotype was indicated by a transcription-independent elevation in glycolytic activity and by increased mitochondrial respiratory potential (OXPHOS) of TNBC cells, accompanied by elevated transcription of mitochondria-encoded OXPHOS genes and of active mitochondria area. The continuous TNFα + IL-1β stimulation has promoted in a glycolysis-dependent manner the activation of p65 (NF-kB), and the transcription and protein expression of the prometastatic and proinflammatory mediators sICAM-1, CCL2, CXCL8 and CXCL1. Moreover, when TNBC cells were stimulated continuously by TNFα + IL-1β in the presence of a glycolysis inhibitor, their conditioned media had reduced ability to recruit monocytes and neutrophils in vivo. Such inflammation-induced metabolic plasticity, which promotes prometastatic cascades in TNBC, may have important clinical implications in treatment of TNBC patients.
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http://dx.doi.org/10.3390/cells10061356 | DOI Listing |
New Microbiol
January 2021
Departamento de Biología Molecular e Histocompatibilidad, Hospital General "Dr. Manuel Gea González", Calzada de Tlalpan 4800, Col. Sección XVI, CP 14080, Ciudad de México, México.
Cervical lymph node tuberculosis (LNTB) is the most common manifestation of extrapulmonary tuberculosis, resulting from the interaction of environmental and genetic factors. The immune response against TB is regulated by several cytokines, which have single nucleotide polymorphisms (SNPs), leading to different levels of expression. The aim of this study was to evaluate the association of LNTB with the TNF, IL8, IL10, IL12B and IFNG gene polymorphisms in Mexican patients.
View Article and Find Full Text PDFLeuk Res Treatment
December 2012
Biological Sciences Institute, Pediatric Hematology Oncology Center (CEONHPE/UPE), Avenida Agamenon Magalhães, Bairro de Santo Amaro, 50100-010 Recife, PE, Brazil.
Alcohol Clin Exp Res
November 2005
Unidad de Medicina Molecular-Departamento de Medicina, Instituto de Neurociencias de Castile and León,Universidad de Salamanca, Spain.
Background: The tumor necrosis factor alpha gene (TNFA) has been recently associated to alcoholic steatohepatitis. We have analyzed the distribution of genotypes and alleles of two polymorphisms at positions -238 and -308 in the promoter region of the TNFA gene in a Spanish male population of alcoholics with and without alcoholic liver cirrhosis.
Methods: 149 male alcoholics (84 without alcoholic liver disease, and 65 with alcoholic liver cirrhosis) and 90 control subjects were included.
J Clin Pathol
January 2004
Department of Transplantation Immunology, St James's University Hospital, Leeds, LS9 7TF, UK.
Aims: To determine whether polymorphisms of the genes encoding donor or recipient interleukin 1alpha (IL-1alpha), tumour necrosis factor alpha (TNFalpha), or IL-4 have any impact on the incidence of acute rejection after renal transplantation.
Methods: All donors and recipients were genotyped for three polymorphisms in the three cytokine genes: IL1A -889, TNFA -308, and IL4 -590.
Results: Statistical analysis of the data obtained revealed no association between the cytokine gene polymorphisms tested and the incidence of post-transplant acute rejection.
Tissue Antigens
May 2003
Hung Kuang University, Institute of Medicine, and Institute of Immunology, Chung Shan Medical University, Taichung, Taiwan, Republic of China.
Type 2 diabetic mellitus (type 2 DM) comprises more than 95% of all Taiwanese patients with DM. Tumor necrosis factor-alpha (TNF-alpha) expression is linked with insulin resistance, and is under strong genetic control. The correlation between TNF promoter genotypes and type 2 DM is still controversial, because discrepancies among different studies exist.
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