Interleukin‐6 and its receptor in cancer

Abstract

Interleukin-6 (IL-6) plays a major role in the response to injury or infection and is involved in the immune response, inflammation, and hematopoiesis. Its deregulation impacts numerous disease states, including many types of cancer. Consequently, modulating IL-6 may be an innovative therapeutic strategy in several diseases. A review of relevant published literature regarding IL-6 and its receptor was performed. In addition, a review of the relevance of this cytokine system to human illness, particularly in cancer, was undertaken. IL-6 is a pleiotropic cytokine that is involved in the physiology of virtually every organ system. Aberrant expression of this cytokine has been implicated in diverse human illnesses, most notably inflammatory and autoimmune disorders, coronary artery and neurologic disease, gestational problems, and neoplasms. In cancer, high levels of circulating IL-6 are observed in almost every type of tumor studied and predict a poor outcome.

IL-6 involvement in epithelial cancers

“…IL-6 binds to a heterodimeric receptor, which contains the ligand-binding IL-6α chain and the common cytokine receptor signal-transducing subunit gp130. IL-6 receptor engagement leads to activation of the JAK family of tyrosine kinases, which then stimulate multiple pathways involving MAPKs, PI3Ks, STATs, and other signaling proteins (2). Given the reported involvement of IL-6 and its downstream targets in the regulation of cell proliferation, survival, and metabolism, it is not surprising that IL-6 signaling has also been implicated in tumorigenesis (3).…”

Significance of TNF-α and IL-6 expression in invasive pituitary adenomas

“…It is generally understood that this mechanism consists of the activation of JAK/STAT and Ras/Erk signaling pathways in tumor cells through the binding of IL-6 to its receptor. Consequently, a large amount of vascular endothelial growth factor is secreted by tumor cells, thus stimulating angiogenesis (Hong et al, 2007). Invasiveness is a major factor related to tumor malignancy.…”

Targeting the inflammatory pathways to enhance chemotherapy of cancer

“…Emphasis has put on a critical role for IL-6 in the immune response, inflammation and hematopoiesis and therapeutic targeting of IL-6 and its receptor in cancer has strong biologic rationale. 123 Ancrile et al stated that oncogenic Ras-induced secretion of IL6 was required for carcinogenesis and IL6 appeared to act in a paracrine fashion to promote angiogenesis and tumor growth. 124 The levels of IL-6 and its receptor increase during carcinogenesis and have been correlated with adverse prognosis.…”

“…124 The levels of IL-6 and its receptor increase during carcinogenesis and have been correlated with adverse prognosis. 123 Sharma et al observed that levels of IL-6 and sgp130 were significantly elevated in patients with advanced colorectal cancer (CRC) and inflammatory markers could predict for clinical outcome. 125 Recent studies have provided evidence for the critical role of the NFκB-IL-6-STAT3 cascade.…”