An overview of the role of interleukin-8 in colorectal cancer

126

Cancer-associated fibroblasts (CAFs) play a key role in cancer progression by contributing to extracellular matrix (ECM) deposition and remodeling, extensive crosstalk with cancer cells, epithelial-to-mesenchymal transition (EMT), invasion, metastasis, and therapy resistance. As metastasis is a main reason for cancer-related deaths, it is crucial to understand the role of CAFs in this process. Colorectal cancer (CRC) is a heterogeneous disease and lethality is especially common in a subtype of CRC with high stromal infiltration. A key component of stroma is cancer-associated fibroblasts (CAFs). To provide new perspectives for research on CAFs and CAF-targeted therapeutics, especially in CRC, we discuss the mechanisms, crosstalk, and functions involved in CAF-mediated cancer invasion, metastasis, and protection. This summary can serve as a framework for future studies elucidating these roles of CAFs.

Section: Caf–tumor Communicationmentioning

confidence: 99%

The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Asif

Longobardi

Hahne

et al. 2021

126

“…The role of tumor necrosis factor-α is in the activation of immune cells and subsequent carcinogenic activity by ERK, NF-kB and PI3K-AKT pathways resulting in increased levels of β-catenin [ 5 , 19 , 20 ]. Via NF-kB, TNFα reduces MUC2 activity with the effect of reducing the production of the mucin layer, which exposes the underlying cell to damage [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

“…IL-8 is responsible for the proliferation and survival of cancer cells, angiogenesis and tumor infiltration, regulating the actions of macrophages, neutrophils, endothelial cells, TRegs and cancer cells. IL-8 acts through AKT, MAPK, STAT-3 intracellular pathways, ERK extracellular pathway and SNAIL, which is a signal that leads to conversion from epithelial to mesenchymal cells necessary for tumor progression [ 10 , 20 ]. Moreover, IL-8 upregulates serine-proteases of ECM, which in turn, are involved in the disruption of the integrity barrier [ 10 ].…”

Section: Resultsmentioning

confidence: 99%

The Complex Network between Inflammation and Colorectal Cancer: A Systematic Review of the Literature

Percario

Panaccio

Mola

et al. 2021

Background: colorectal cancer (CRC) has a multifactorial etiology which comprises microbiota, genetic predisposition, diet, environmental factors, and last but not least, a substantial contribution by inflammation. The aim of this study is to conduct a systematic review of the literature regarding the strong link between inflammation and colorectal cancer. Methods: A systematic review of the literature on PubMed (Medline), Scopus, Cochrane and EMBase databases was performed, following the PRISMA 2020 guidelines. Each paper was reviewed by two groups of researchers in a single-blind format by using a pre-planned Microsoft© Excel® grid. Results: Using automated research filters, 14,566 studies were included, but 1% was found significant by the reviewers. Seventy pathways of inflammation were described in the sequence of inflammation-carcinogenesis, and anti-tumorigenic molecules were also found. Conclusion: several studies suggest a strong role of inflammation in the tumorigenesis of colorectal cancer through different pathways: this may have a diagnostic and clinical role and also therapeutic purpose in preventing carcinogenesis by treating inflammation. In vitro tests support this theory, even if many other clinical trials are necessary. The present paper was registered in the OpenScience Framework registry (Identifier: DOI 10.17605/OSF.IO/2KG7T).

“…In another study, high serum levels of IL-6 were associated with the tumor stage, tumor size, tumor metastasis, and survival of patients [ 42 ]. Increased serum levels of IL-8 because of polymorphisms in the IL-8/CXCR2 genes were associated with disease progression, disease recurrence, and drug resistance [ 43 , 44 , 45 , 46 ]. Furthermore, patients with COPD with frequent exacerbations were reported to have high levels of inflammatory markers, such as CRP [ 47 ], fibrinogen [ 47 ], IL-6 [ 48 ], soluble tumor necrosis factor-α receptors [ 37 , 49 , 50 ], and osteoprotegrin [ 37 ], which have been shown to be associated with the survival of patients with colorectal cancer [ 39 , 40 , 41 , 42 , 51 , 52 , 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Chronic Obstructive Pulmonary Disease and Its Acute Exacerbation before Colon Adenocarcinoma Treatment Are Associated with Higher Mortality: A Propensity Score-Matched, Nationwide, Population-Based Cohort Study

Chen

et al. 2021

Purpose: To investigate whether chronic obstructive pulmonary disease (COPD) and COPD severity (acute exacerbation of COPD (AECOPD)) affect the survival outcomes of patients with colon adenocarcinoma receiving standard treatments. Methods: From the Taiwan Cancer Registry Database, we recruited patients with clinical stage I–III colon adenocarcinoma who had received surgery. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into COPD and non-COPD (Group 1 and 2) groups through propensity score matching. Results: In total, 1512 patients were eligible for further comparative analysis between non-COPD (1008 patients) and COPD (504 patients) cohorts. In the multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) for all-cause mortality for Group 1 compared with Group 2 was 1.17 (1.03, 1.29). In patients with colon adenocarcinoma undergoing curative resection, the aHRs (95% CIs) for all-cause mortality in patients with hospitalization frequencies of ≥1 and ≥2 times for AECOPD within 1 year before adenocarcinoma diagnosis were 1.08 (1.03, 1.51) and 1.55 (1.15, 2.09), respectively, compared with those without AECOPD. Conclusion: In patients with colon adenocarcinoma undergoing curative resection, COPD was associated with worse survival outcomes. Being hospitalized at least once for AECOPD within 1 year before colon adenocarcinoma diagnosis was an independent risk factor for poor overall survival in these patients, and a higher number of hospitalizations for AECOPD within 1 year before diagnosis was associated with poorer survival. Our study highlights the importance of COPD management, particularly the identification of frequent exacerbators and the prevention of AECOPD before standard colon adenocarcinoma treatments are applied.