C-Reactive Protein Signaling Pathways in Tumor Progression

Abstract

Many cancers arise from sites of chronic inflammation, which creates an inflammatory microenvironment surrounding the tumor. Inflammatory substances secreted by cells in the inflammatory environment can induce the proliferation and survival of cancer cells, thereby promoting cancer metastasis and angiogenesis. Therefore, it is important to identify the role of inflammatory factors in cancer progression. This review summarizes the signaling pathways and roles of C-reactive protein (CRP) in various cancer types, including breast, liver, renal, and pancreatic cancer, and the tumor microenvironment. Mounting evidence suggests the role of CRP in breast cancer, particularly in triple-negative breast cancer (TNBC), which is typically associated with a worse prognosis. Increased CRP in the inflammatory environment contributes to enhanced invasiveness and tumor formation in TNBC cells. CRP promotes endothelial cell formation and angiogenesis and contributes to the initiation and progression of atherosclerosis. In pancreatic and kidney cancers, CRP contributes to tumor progression. In liver cancer, CRP regulates inflammatory responses and lipid metabolism. CRP modulates the activity of various signaling molecules in macrophages and monocytes present in the tumor microenvironment, contributing to tumor development, the immune response, and inflammation. In the present review, we overviewed the role of CRP signaling pathways and the association between inflammation and cancer in various types of cancer. Identifying the interactions between CRP signaling pathways and other inflammatory mediators in cancer progression is crucial for understanding the complex relationship between inflammation and cancer.

mCRP-Induced Focal Adhesion Kinase-Dependent Monocyte Aggregation and M1 Polarization, Which Was Partially Blocked by the C10M Inhibitor

“…In this study we showed that pre-incubation with the FAK inhibitor I (CAS 4506-66-5 VWR) for 24 h prior to treatment with mCRP abrogated the U937 aggregation, indicating a FAK-dependent mechanism. Previous studies have demonstrated that CRP binding through α2β1 integrins activated FAK, and subsequently MAP kinase pathways, resulting in increased breast cancer cells adhesion and invasion [ 18 ]. In macrophages, FAK modulation is known to be critical for initiation and perpetuation of adhesion and motility, and although interactions through integrin activation predispose macrophage to M1 phenotypical polarization, our study is the first to show a direct link between mCRP, FAK, and monocyte aggregation, and subsequent polarization to the pro-inflammatory phenotype [ 19 , 20 ].…”

Prognostic Biomarkers of Systemic Inflammation in Non-Small Cell Lung Cancer: A Narrative Review of Challenges and Opportunities

“…It is an acute-phase protein synthesized by the liver in response to inflammatory stimuli. It exerts pro-inflammatory responses that are associated with tumour invasion and plays a role in promoting tumour immune escape [51].…”

The Relationship Between Neutrophil Lymphocyte Ratio and C-Reactive Protein with Depression and Quality of Life in Non-Small-Cell Lung Cancer Patient

“…CRP can bind to a variety of exogenous and endogenous ligands that are exposed on the cell membrane in the presence of damage, necrosis or apoptotic cells. CRP strongly activates the classical complement pathway which further amplifies tissue damage and potentially makes the disease more severe [41].…”

“…CRP interacting with TLRs leads to signaling pathways that increase the production of pro-inflammatory cytokines including TNF-α, IL-1, and IL-6 in macrophages and monocytes. These cytokines cause further tumor growth, angiogenesis, tumor cell survival, proliferation, and tumor cell resistance to apoptosis [41]. This process will trigger further cancer progression and metastasis, and indirectly affect the increase and worsening of patient symptoms and complaints and may risk contributing to reducing the quality of life of lung cancer patients.…”