Tumor Cell Adhesion to Endothelial Cells Is Increased by Endotoxin via an Upregulation of β-1 Integrin Expression

Andrews, Emmet; Wang, J.H.; Winter, Desmond C.; Laug, Walter E.; Redmond, H. P.

doi:10.1006/jsre.2001.6090

Cited by 41 publications

(29 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HUVECs were grown in M199 (Invitrogen) supplemented with 20% heat-inactivated fetal bovine serum, 20 g/ml endothelial cell growth supplement (Sigma-Aldrich, St. Louis, MO), 100 U/ml penicillin, 100 g/ml streptomycin, and 2 mM L-glutamine. The identification of HUVECs was confirmed by their polygonal morphology and detection of their immunoreactivity for factor VIII-related antigens (Andrews et al, 2001). PC-3M cells were cultured in RPMI medium 1640 containing 10% heat-inactivated fetal bovine serum, 100 U/ml penicillin, and 100 g/ml streptomycin in a humidified incubator with 5% CO 2 in air at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Role of Vimentin in the Inhibitory Effects of Low-Molecular-Weight Heparin on PC-3M Cell Adhesion to, and Migration through, Endothelium

Pan¹,

Lei²,

Teng³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Low-molecular-weight heparin (LMWH) has been used in cancer patients with venous thromboembolic complications, resulting in a higher survival rate and an inhibitory action on experimental metastasis. In the present study, human umbilical vein endothelial cells (HUVECs) were treated with LMWH for 24 h. We found that the resulting HUVECs could significantly inhibit the highly metastatic human prostate cancer cell line (PC-3M) in terms of its adhesion to the endothelium and migration across the endothelium, according to scanning electron microscopy. We also determined the elevated levels of endothelial intercellular Ca 2ϩ concentration after the adhesion of PC-3M cells to HUVECs was greatly reduced by incubation with LMWH. Using proteomics, we surveyed the global protein changes in HUVECs after LMWH treatment and identified four down-regulated proteins that were possible isoforms of cytoskeletal vimentin intermediate filaments, cartilage-derived Ctype lectin, and serine/threonine protein phosphatase 1␤ (PP-1B). LMWH affected the morphology of vimentin and the expression levels of ␣ v integrin and PP-1B in HUVECs bound to PC-3M cells. Vimentin assists in the adhesion of PC-3M cells, which was confirmed by short interfering RNA experiments. Furthermore, the direct binding of purified vimentin protein with LMWH was detected with surface plasmon resonance methods. However, when we used fluorescence-labeled heparin for 24 h to identify whether this binding occurred within cells, heparin was distributed principally around endothelial cells. Taken together, these findings suggest that the monoincubation of LMWH with HUVECs could inhibit PC-3M cell adhesion to, and migration through, endothelium. LMWH's regulation of vimentin plays a role in the antimetastatic action.

show abstract

Section: Methodsmentioning

confidence: 99%

Role of Vimentin in the Inhibitory Effects of Low-Molecular-Weight Heparin on PC-3M Cell Adhesion to, and Migration through, Endothelium

Pan¹,

Lei²,

Teng³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…NF-κB promotes expression of various adhesion factors-including galectin-3 20,21 -that can aid tumor cell-endothelium adhesion; moreover, NF-κB in cancer cells further aids their metastatic capacity by inducing expression of matrix proteases. [22][23][24][25][26][27][28] It is thus intriguing that both aspirin and salicylate, in the high clinical concentrations that achieve the best benefit in rheumatic disorders, can suppress activation of NF-κB by blocking the kinase activity of its upstream activator IκB kinase-β (IKK-β); these drugs are competitive inhibitors of adenosine triphosphate binding to IKK-β. 29,30 This presumably accounts for the antimetastatic activity of aspirin-not shared by indomethacin-reported in a rodent model of metastasis.…”

Section: Preventing Metastasismentioning

confidence: 99%

Toward a Core Nutraceutical Program for Cancer Management

McCarty

Block

2006

Integr Cancer Ther

View full text Add to dashboard Cite

As previously suggested, it may be feasible to impede tumorevoked angiogenesis with a nutraceutical program composed of glycine, fish oil, epigallocatechin-3-gallate, selenium, and silymarin, complemented by a low-fat vegan diet, exercise training, and, if feasible, a salicylate and the drug tetrathiomolybdate. It is now proposed that the scope of this program be expanded to address additional common needs of cancer patients: blocking the process of metastasis; boosting the cytotoxic capacity of innate immune defenses (natural killer [NK] cells); preventing cachexia, thromboembolism, and tumor-induced osteolysis; and maintaining optimal micronutrient status. Modified citrus pectin, a galectin-3 antagonist, has impressive antimetastatic potential. Mushroom β-glucans and probiotic lactobacilli can amplify NK activity via stimulatory effects on macrophages. Selenium, β-carotene, and glutamine can also increase the number and/or cytotoxic activity of NK cells. Cachectic loss of muscle mass can be opposed by fish oil, glutamine, and β-hydroxy-β-methylbutyrate. Fish oil, policosanol, and vitamin D may have potential for control of osteolysis. High-dose aspirin or salicylates, by preventing NF-κB activation, can be expected to aid prevention of metastasis and cachexia while down-regulating osteolysis, but their impacts on innate immune defenses will not be entirely favorable. A nutritional insurance formula crafted for the special needs of cancer patients can be included in this regimen. To minimize patient inconvenience, this complex core nutraceutical program could be configured as an oil product, a powder, and a capsule product, with the nutritional insurance formula provided in tablets. It would be of interest to test this program in nude mouse xenograft models.

show abstract

“…Contemporary experimental evidence suggests that TLRs have important roles in tumourigenesis (Killeen et al, 2008). Lipopolysaccharide, a putative ligand for TLR4, may promote tumour progression by acting directly on cancer cells, resulting in increased tumour cell -endothelial cell adhesion, tumour cell -extracellular matrix adhesion, and tumour cell -extracellular matrix invasion through NF-kB-mediated upregulation of b-1 integrin (Andrews et al, 2001;Wang et al, 2003). Helicobacter pylori acting through TLR2/TLR9 on gastric epithelial cells activated both Src and NF-kB, resulting in an increased expression of cyclooxygenase-2 (Cox-2), which may contribute to gastric cancer progression (Chang et al, 2004).…”

mentioning

confidence: 99%

High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer

et al. 2010

View full text Add to dashboard Cite

BACKGROUND: The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC). METHODS: The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed. RESULTS: Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P ¼ 0.0001, P ¼ 0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15 -4.07; P ¼ 0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31 -4.13; P ¼ 0.0038 and HR: 3.03; 95% CI: 1.67 -5.48; P ¼ 0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27 -3.99; P ¼ 0.0053 and HR: 2.97; 95% CI: 1.64 -5.38; P ¼ 0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99 -3.55; P ¼ 0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01 -3.67; P ¼ 0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17 -4.33; P ¼ 0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS. CONCLUSION: Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC.

show abstract

Tumor Cell Adhesion to Endothelial Cells Is Increased by Endotoxin via an Upregulation of β-1 Integrin Expression

Cited by 41 publications

References 20 publications

Role of Vimentin in the Inhibitory Effects of Low-Molecular-Weight Heparin on PC-3M Cell Adhesion to, and Migration through, Endothelium

Role of Vimentin in the Inhibitory Effects of Low-Molecular-Weight Heparin on PC-3M Cell Adhesion to, and Migration through, Endothelium

Toward a Core Nutraceutical Program for Cancer Management

High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer

Contact Info

Product

Resources

About