Chronic Stress Mediates Inflammatory Cytokines Alterations and Its Role in Tumorigenesis.

Abstract

Introduction: Prolonged psychological stress is closely associated with cancer due to its role in promoting the release of stress hormones through the sustained activation of the sympathetic-adrenal-medullary system. These hormones interact with receptors on inflammatory cells, leading to the activation of key signaling pathways, including the transcription factors signal transducer and activator of transcription 3 (STAT-3) and kappa-light-chain-enhancer of activated B cells (NF-κB). These factors drive the production of pro-inflammatory substances, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which can influence the initiation and progression of cancer.

Purpose: This article aims to summarize how the chronic inflammatory environment induced by chronic stress promotes the initiation, progression, and invasion of cancer. By enhancing our understanding of the complex mechanisms through which stress contributes to cancer, we hope to identify new targets for cancer prevention and treatment.

Conclusion: Chronic stress establishes an inflammatory microenvironment by activating STAT-3 and NF-κB in inflammatory cells. This ongoing inflammation further enhances the activity of these transcription factors, which serve multiple roles: they act as pro-inflammatory agents in inflammatory cells, maintaining chronic inflammation; as oncogenic transcription factors in premalignant cells, promoting cancer initiation; and as pro-differentiation transcription factors in tumor-infiltrating immune cells, facilitating cancer progression. Additionally, the impact of chronic stress varies among different cancer types and individual responses to stress, highlighting the complexity of stress-related cancer mechanisms. Ultimately, this dynamic interplay creates a feedback loop involving IL-6, STAT-3, and TNF-α-NF-κB within the tumor microenvironment, mediating the intricate interactions between inflammation, immunity, and cancer.