Increased level of interleukin-8 (IL-8) and CXCR2 on tumours and in the tumour microenvironment has been associated with CRC growth, progression and recurrence in patients.
The RNF183-IL-8 axis is responsible for the resistance of CRC cells to the MEK1/2 inhibitor trametinib and may serve as a candidate target for combined therapy for CRC.
In addition to promoting angiogenesis, proliferation, invasion, migration, and the survival of colorectal cancer (CRC) cells, CXCL8 and its receptors have also been known to induce the epithelial-mesenchymal transition (EMT) of CRC cells, to help them to escape host immunosurveillance as well as to enhance resistance to anoikis, which promotes the formation of circulating tumor cells (CTCs) and their colonization of distant organs.
The aim of the study was to describe the levels of circulating monocyte/macrophage pro-inflammatory cytokines (TNF-alpha, IL-1beta IL-6, and IL-8) and an anti-inflammatory cytokine (IL-10) in inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients and healthy controls.
This response was attenuated by treating TAMs with the KCNN4 channel-specific inhibitor, 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34), which suggested that KCNN4 channels may be involved in inducing the secretion of IL-6 and IL-8 by TAMs and improving CRC cell invasiveness.
Cell-free DNA derived from cancer cells facilitates tumor malignancy through Toll-like receptor 9 signaling-triggered interleukin-8 secretion in colorectal cancer.
Taken together, these results implicated the important role of PRL-3 in glycolysis metabolism through improving IL-8 secretion in colorectal cancer cells, and PRL-3 mediated glycolysis contributed to the promotion of cancer metastasis.
We conclude that 1) colorectal carcinogenesis is accompanied by increased synthesis and release of proinflammatory cytokines such as IL-6 and IL-8; 2) simvastatin therapy results in a decrease in serum level of proinflammatory cytokines, especially IL-6 in CRC and 3) simvastatin inhibits release of IL-8 and IL-6 from colorectal cell lines.
The most promising cytokine to detect CRC was interleukin 8, and the most promising circulating proteins were CA11-19 glycoprotein and DC-SIGN/DC-SIGNR.
Protein levels of IL-8 and cyclin D1 (CCND1), the two important molecules in the IL-8 pathway, were positively correlated with Gankyrin expression in human CRC specimens.
SMAD4 knockdown from human colorectal cancer cells upregulated the expression of CXCL1 and CXCL8, which recruited neutrophils to colorectal cancer tumor via CXCR2.
Top candidates were tested <i>in vitro</i> on the CRC epithelial cell line HT29/c1 for their potential to inhibit key aspects of BFT activity, being epithelial morphology changes, E-cadherin cleavage (a marker for barrier function) and increased IL-8 secretion.
We have used in situ hybridisation and immunohistochemistry to determine whether IL-8 mRNA and protein, respectively, are produced by human colorectal carcinoma cells in vivo.
Activation of GPR120 signaling in human CRC promotes angiogenesis in vitro and in vivo, largely by inducing the expression and secretion of proangiogenic mediators such as vascular endothelial growth factor (VEGF), interleukin-8 and cyclooxygenase-2-derived prostaglandin E2.
CRC patients had higher levels of IL-6 (p = 0.002) and IL-8 (p = 0.038) expression than healthy volunteers did; and higher IL-6 and IL-8 expression was also found to signify a higher risk of recurrence.
Further double IHC identified the co-expression of IL-8 receptors (IL-8RA and IL-8RB) with CD34 positive tumor-associated microvessels in both the adenomas and CRCs.
Furthermore, NF-kappaB may contribute to the progression of CRC by regulating the expression of diverse target genes that are involved in cell proliferation (Cyclin D1), angiogenesis (VEGF, IL-8, COX2), and metastasis (MMP9).