While the aberrant expression of RDGN is involved in the proliferation, apoptosis, angiogenesis, and metastasis of tumors via interacting with different cytokine-related signals, such as CXCL8, IL-6, TGF-β, FGF, and VEGF, in a cell- or tissue-dependent manner.
When comparing the expression of cytokines in OS patients with different clinical parameters, cases with osteoblastic subtype revealed increased level of IL-6 than patients with other subtypes (p < 0.05); cases with metastasis demonstrated significantly higher level of TNF-α than those without metastasis (p < 0.05), whereas OS patients whose tumor size were bigger than 8 cm presented elevated levels of IL-8 and TNF-α than those with small tumor size (p < 0.05 and p < 0.05, respectively).
When a co-culture system of A549 cells and bone marrow-derived cells (HS-5) was established, it was shown that HS-5 cells promoted the proliferation and migration of A549 cells, and metastasis and osteoclast-related factors IL-6 and IL-8 were increased in the A549 and HS-5 cells.
We selected the clones with the highest and lowest expression level of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF)/vascular permeability factor or interleukin-8 (IL-8) in the highly tumorigenic and metastatic human UC cell line 253J B-V. Tumorigenicity and production of spontaneous lymph node metastases were evaluated 1, 2, 4, 8 and 12 weeks after orthotopic implantation of each specific expression clone into the urinary bladder of athymic nude mice.
We previously demonstrated the importance of interleukin-8 (IL-8) as a mediator of angiogenesis, tumorigenicity, and metastasis of transitional cell carcinoma (TCC) of the bladder.
We found that BRAF inhibition induces invasion and metastasis in RAS mutant melanoma cells through a mechanism mediated by the reactivation of the MEK (mitogen-activated protein kinase kinase)-ERK pathway, increased expression and secretion of interleukin 8, and induction of protease-dependent invasion.
We evaluated whether IL-8 expression by human prostate cancer growing within the prostate of athymic nude mice regulates tumor angiogenesis, growth, and metastasis.
We analyzed the gene expression of β-catenin, c-Myc and IL-8 in human HCC tissue by RT-PCR and immunohistochemistry and analyzed five variously differentiated HCC cell lines by Western blotting and migration and invasion assays to find markers for HCC diagnosis and HCC metastasis. mRNA expression of β-catenin was significantly higher in the tumor area compared to the non-tumor area and was more abundant in specimens of late-stage HCC.
We also observed that patients with distant metastasis showed a significantly higher plasma level of IL-8 in relation to patients without distant metastasis.
Using immunohistochemistry, we found that thyroid epithelial cancerous, but not normal, cells stained positive for IL-8, whose levels correlated with lymph-nodal metastases.
Upon comparing to Panc-1 cells, we found that the dominant expression of the IL-8 gene in MiaPaCa-2 cells resulted in an aggressive behavior towards the processes of cell invasion and metastasis.
Transgenic overexpression of FOXC1 in HCC cells with IL8 knockdown increased the numbers of metastases formed in mice compared with cells without FOXC1 overexpression.
Together, these results demonstrate the key roles of B cells within the bladder tumor microenvironment that increase the BCa metastasis and may help us to develop the potential therapies via targeting these newly identified IL-8/AR/MMPs signals to better battle the BCa progression.
Together, our results indicated that IL-8 triggered ovarian cancer cells migration partly through Wnt/β-catenin pathway mediated EMT, and IL-8 may be an important molecule in the invasion and metastasis of ovarian cancer.
To directly determine the role of IL-8 in the growth and metastasis of pancreatic cancer, FG cells were transfected with IL-8 sense or antisense oligonucleotide expression vectors.
Thus, transendothelial migration and lung metastasis development decreased by approximately 50%, showing that targeting IL-8 in melanoma cells has the potential to decrease metastasis development by disrupting interaction with neutrophils.
This TGF-beta1-induced IL-8 expression could be an amplification cascade responsible for overexpression of IL-8 in human melanoma and one of potential mechanisms by which TGF-beta1 promotes angiogenesis, growth, and metastasis of human melanoma.
This review focuses on recent advances in understanding how an established tumor can initiate an inflammatory response via the release of pro-inflammatory mediators, such as IL-6 and IL-8, and their roles in cancer metastasis.
These studies provide the first evidence that LPA promotes lymphangiogenesis and induces IL-8 production in LECs; we also reveal a possible new role of LPA in the promotion of tumor progression, as well as metastasis, in different cancer types.
These studies demonstrate that IL-8 expression enhances angiogenic activity through the induction of matrix metalloproteinase type 9 and subsequently regulates the tumorigenesis and production of spontaneous metastases of human TCC.
These results suggest that overexpression of TrkB and activation of mitogen-activated protein kinase and AP-1, which may in turn induce the expression of vascular endothelial growth factor and interleukin 8, may mediate the cardinal clinical features of locally aggressive growth and metastasis of pancreatic cancer.
These results identify IL-6 and CXCL8 as primary mediators of OS lung tropism and suggest pleiotropic, redundant mechanisms by which they might effect metastasis.