Lymphotoxin, NF-ĸB, and Cancer: The Dark Side of Cytokines

Abstract

Cytokines have been implicated in a variety of physiological processes involving lymphoid tissue development, lymphocyte activation, and control of regenerative processes such as wound healing. The first characterization of a cytokine implicated in abolishing or killing tumor cells – the tumor necrosis factor (TNF) – fostered and boosted a completely new field of research that in addition to cancer research started to generate an overwhelming amount of knowledge in immunology, various pathological processes, and other fields of research. Due to the complex networks and versatile functions of cytokines, it soon became clear that cytokines can possess diametric functions in various biological processes. As for tumor research it was shown that some cytokines – depending on the type of organ, the time of action, gender, and the cellular environment – can have either pro- or anticarcinogenic action. For those cytokines reported to be procarcinogenic, this could be accomplished by directly acting as oncogenes or generating an inflammatory environment that is procarcinogenic. Here we review a novel role for TNF family members – in particular lymphotoxin (LT) α and β – in physiology and in driving tumorigenesis, with special focus on the liver. We believe that recent findings on this particular cytokine might have strong implications for the therapy of liver cancer or other inflammation-induced cancer types.

Lymphotoxin‐β receptor‐NIK signaling induces alternative RELB/NF‐κB2 activation to promote metastatic gene expression and cell migration in head and neck cancer

“…Many immune regulatory cytokines are produced in the lymph nodes, which nurture and modulate immune cell proliferation, maturation, migration, and defense functions. Among these, Lymphotoxin‐β (LTβ) is one of the crucial cytokines produced by lymphocytes and lymphoid tissues . LTβ is an anchored transmembrane protein of 244 aa (18.5 KDa), that can form soluble heterotrimers (LTα1β2, or LTα2β1), which are shed from the cell surface by proteolytic cleavage.…”

Clinical aspects and polymorphisms in the LTA, TNFA, LTB genes and association with dental implant loss

“…The proteins of the LTA , LTB, and TNFA genes are involved in several pathophysiological processes, especially in the complex network of the local inflammatory cascade, inducing vasodilation and depletion of leukocyte cells. However, a change on their expression may generate an unfavorable and hazardous environment to the organism …”

“…4,11,[13][14][15]41,50 To the author's knowledge, there is no study with LTA, TNFA, and LTB genes and to the organism. 17,51,52 Polymorphisms in those genes are responsible for the modulation of numerous diseases. 27 Polymorphisms in the LTA gene have already been associated with distinct pathologies.…”

Role of traditional chinese medicine and its chemical components in anti-tumor metastasis

“…[86][87][88] NF-κB can accelerate the adhesion of tumor cells to epithelial cells and matrix, induce tumor cells to generate protease so as to degrade extracellular matrix, and promote vascularization. [89,90] Sliva et al, found that lucid ganoderma exerted the inhibiting effects on the migration of high invasive non-estrogen receptor-dependent breast cancer cell via inhibiting NF-κB signal pathway.…”