scholarly journals Tumor necrosis factor superfamily 15 promotes lymphatic metastasis via upregulation of vascular endothelial growth factor‐C in a mouse model of lung cancer

2018 ◽  
Vol 109 (8) ◽  
pp. 2469-2478 ◽  
Author(s):  
Tingting Qin ◽  
Dingzhi Huang ◽  
Zhujun Liu ◽  
Xiaoling Zhang ◽  
Yanan Jia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Mouse Model ◽  
Tumor Necrosis ◽  
Vascular Endothelial ◽  
Factor C ◽  
Endothelial Growth Factor ◽  
Necrosis Factor

scholarly journals The relationship between chemokines CCL2, CCL3, and CCL4 with the tumor microenvironment and tumor-associated macrophage markers in colorectal cancer

Tumor Biology ◽  
2018 ◽  
Vol 40 (11) ◽  
pp. 101042831881005 ◽  
Author(s):  
Marjorie De la Fuente López ◽  
Glauben Landskron ◽  
Daniela Parada ◽  
Karen Dubois-Camacho ◽  
Daniela Simian ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Inflammatory Mediators ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Vascular Endothelial ◽  
Factor Α ◽  
Endothelial Growth Factor ◽  
Necrosis Factor

A complex network of chemokines can influence cancer progression with the recruitment and activation of hematopoietic cells, including macrophages to the supporting tumor stroma promoting carcinogenesis and metastasis. The aim of this study was to investigate the relation between tissue and plasma chemokine levels involved in macrophage recruitment with tumor-associated macrophage profile markers and clinicopathological features such as tumor–node–metastases stage, desmoplasia, tumor necrosis factor-α, and vascular endothelial growth factor plasma content. Plasma and tumor/healthy mucosa were obtained from Chilean patients undergoing colon cancer surgery. Chemokines were evaluated from tissue lysates (CCL2, CCL3, CCL4, CCL5, and CX3CL1) by Luminex. Statistical analysis was performed using Wilcoxon match-paired test ( p  < 0.05). Macrophage markers (CD68, CD163, and iNOS) were evaluated by immunohistochemistry samples derived from colorectal cancer patients. Correlation analysis between chemokines and macrophage markers and clinicopathological features were performed using Spearman’s test. Plasmatic levels of chemokines and inflammatory mediators’ vascular endothelial growth factor and tumor necrosis factor-α were evaluated by Luminex. Tumor levels of CCL2 (mean ± standard deviation = 530.1 ± 613.9 pg/mg), CCL3 (102.7 ± 106.0 pg/mg), and CCL4 (64.98 ± 48.09 pg/mg) were higher than those found in healthy tissue (182.1 ± 116.5, 26.79 ± 22.40, and 27.06 ± 23.69 pg/mg, respectively p < 0.05). The tumor characterization allowed us to identify a positive correlation between CCL4 and the pro-tumor macrophages marker CD163 ( p  = 0.0443), and a negative correlation of iNOS with desmoplastic reaction ( p  = 0.0467). Moreover, we identified that tumors with immature desmoplasia have a higher CD163 density compared to those with a mature/intermediated stromal tissue ( p  = 0.0288). Plasmatic CCL4 has shown a positive correlation with inflammatory mediators (tumor necrosis factor-α and vascular endothelial growth factor) that have previously been associated with poor prognosis in patients. In conclusion High expression of CCL4 in colon cancer could induce the infiltration of tumor-associated macrophages and specifically a pro-tumor macrophage profile (CD163+ cells). Moreover, plasmatic chemokines could be considered inflammatory mediators associated to CRC progression as well as tumor necrosis factor-α and vascular endothelial growth factor. These data reinforce the idea of chemokines as potential therapeutic targets or biomarker in CRC.

scholarly journals Gossypin, a pentahydroxy glucosyl flavone, inhibits the transforming growth factor beta-activated kinase-1-mediated NF-κB activation pathway, leading to potentiation of apoptosis, suppression of invasion, and abrogation of osteoclastogenesis

Blood ◽  
2007 ◽  
Vol 109 (12) ◽  
pp. 5112-5121 ◽  
Author(s):  
Ajaikumar B. Kunnumakkara ◽  
Asha S. Nair ◽  
Kwang Seok Ahn ◽  
Manoj K. Pandey ◽  
Zhengfang Yi ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Vascular Endothelial ◽  
Gene Products ◽  
Activation Pathway ◽  
Regulated Gene Expression ◽  
Endothelial Growth Factor ◽  
Necrosis Factor

Abstract Gossypin, a flavone originally isolated from Hibiscus vitifolius, has been shown to suppress angiogenesis, inflammation, and carcinogenesis. The mechanisms of these activities, however, are unknown. Because nuclear factor-κB (NF-κB) is associated with inflammation, carcinogenesis, hyperproliferation, invasion, and angiogenesis, we hypothesized that gossypin mediates its effects through modulation of NF-κB activation. In the present study, we demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-κB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-κB activation in tumor cells was also inhibited by this flavone. Inhibition of IκBα kinase by gossypin led to the suppression of IκBα phosphorylation and degradation, p65 nuclear translocation, and NF-κB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain–like interleukin-1β–converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor–induced cellular invasion, abrogated receptor activator of NF-κB ligand–induced osteoclastogenesis, and vascular endothelial growth factor–induced migration of human umbilical vein endothelial cells. Overall, our results demonstrate that gossypin inhibits the NF-κB activation pathway, which may explain its role in the suppression of inflammation, carcinogenesis, and angiogenesis.

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