IL-18 regulates IL-1<i>β</i>-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1

Vidal‐Vanaclocha, Fernando; Fantuzzi, Giamila; Mendoza, Lorea; Fuentes, Angela M.; Anasagasti, Miren J.; Martín, Javier; Carrascal, Teresa; Walsh, Patrick; Reznikov, Leonid L.; Kim, Soo Hyun; Novick, Daniela; Rubinstein, Menachem; Dinarello, Charles A.

doi:10.1073/pnas.97.2.734

Cited by 315 publications

(261 citation statements)

References 34 publications

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“…Previously, we have reported that hepatic infiltration of B16M melanoma cells leads to a diffuse proinflammatory activation of HSE cells involving vascular cell adhesion molecule-1 expression 7 and cytokine release. 30 Here we show that tumor-activated HSE cells also express CD31 and CD34; however, HSE cell migration only occurred towards avascular micrometastases containing a high density of activated HSCs and not towards non-HSC-containing metastases. Both activated HSCs and HSE cells colocalized, and their densities consistently were correlated with the development of wellvascularized metastases.…”

Section: Discussionmentioning

confidence: 95%

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Proangiogenic role of tumor-activated hepatic stellate cells in experimental melanoma metastasis

2003

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Myofibroblasts infiltrate malignant liver tumors, although their pathogenic implications are unclear. Immunohistochemical detection of ␣-smooth muscle actin, glial fibrillary acidic protein (GFAP), and CD31 and CD34 expression was used to analyze the contribution of myofibroblasts to angiogenesis in hepatic metastasis produced by intrasplenically-injected B16 melanoma (B16M). Because activated hepatic stellate cells (HSCs) are oxygen-sensing myofibroblasts producing vascular endothelial growth factor (VEGF), the effect of B16M and human A375 melanoma supernatants on VEGF production by immortalized rat HSC line T6 and primary cultured human HSCs also was studied under an hypoxic atmosphere mimicking a tumor microenvironment. Myofibroblast infiltration preceded endothelium recruitment in avascular micrometastasis and generated specific stroma for sinusoidal-type and portal-type angiogeneses. Thereafter, myofibroblasts and endothelial cells colocalized within both angiogenic patterns and their numerical densities correlated with metastasis development. Myofibroblasts often were GFAPpositive, suggesting an HSC origin. Melanoma supernatants stimulated VEGF messenger RNA and protein synthesis by HSCs. These effects were potentiated by hypoxia. VEGF up-regulation was accompanied by increased expression of cyclooxygenase type 2 (COX-2) and PGE2 synthesis. HSC production of VEGF decreased under COX-2 inhibition, whereas it was increased by exogenous PGE2. The high VEGF expression in HSCs induced by melanoma factors and hypoxia resulted in mitogenic, antiapoptotic, and motogenic stimulation of both murine hepatic sinusoidal endothelium and human umbilical vein endothelium. In conclusion, temporal and positional relationships evolve between myofibroblast and endothelium recruitment during metastasis development. Mechanistically, hypoxic induction of VEGF in tumor-activated HSCs may create a proangiogenic microenvironment, facilitating endothelial cell recruitment and survival during hepatic metastasis transition from an avascular to a vascular stage. (HEPATOLOGY 2003;37:674-685.)

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Section: Discussionmentioning

confidence: 95%

“…Interestingly, the majority of hepatic metastases in the present model are interleukin-1-dependent. 30 Interleukin 1␤ up-regulates COX-2 activity in many cellular systems including HSCs. 37 Therefore, it is possible that angiogenesis of interleukin-1-dependent metastases is regulated in part by COX-2 activity.…”

Section: Discussionmentioning

confidence: 99%

Proangiogenic role of tumor-activated hepatic stellate cells in experimental melanoma metastasis

2003

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“…Angiogenesis plays an important role in tumour growth and is associated with a poor outcome in patients with GI tumours (Tanigawa et al, 1997;Fondevila et al, 2004). In addition, interleukin (IL) -1 and -6 network is upregulated (Vidal-Vanaclocha et al, 2000;Miki et al, 2004). Interleukin 1 is involved in the development of metastasis in animal studies and IL-6, apart from being a growth factor, promotes resistance to apoptosis (Vidal-Vanaclocha et al, 1994Chauhan et al, 1997;Frassanito et al, 2001;Jee et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

C-reactive protein as a predictor of prognosis following curative resection for colorectal liver metastases

et al. 2007

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There is increasing evidence that systemic inflammatory response has a positive correlation with a poorer outcome in patients undergoing resection for solid tumours. The aim of this study was to analyse the impact of an elevated C-reactive protein (CRP), an outcome following curative resection for colorectal liver metastases. One hundred and seventy patients who underwent curative resection for colorectal liver metastases were included in the study. Laboratory measurements of haemoglobin, white cell, platelets, albumin and CRP were taken on the day before surgery. Elevated CRP (410 mg l À1 ) was present in 54 (31.8%) patients. The median survival of patients with an elevated CRP was 19 months (95% CI 7.5 -31.2 months) compared to 42.8 months (95% CI 33.2 -52.5 months) for those with a normal CRP, P ¼ 0.004. Similarly, when assessing disease-free survival, patients with an elevated CRP had poorer disease-free survival (median of 11.8 months (95% CI 6.4 -17.3) compared to median of 15.1 months (95% CI 11.1 -19.1)), P ¼ 0.043. The result of the study showed that an elevated preoperative CRP is a predictor of poor outcome in patients undergoing curative resection for colorectal liver metastases.

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“…Although IL-18 can enhance the immune response, it was recently reported that tumors could counterattack the immune system by secreting IL-18 (Cho et al, 2000). The serum IL-18 concentration was reported to be higher in metastatic cancer patients than in early cancer patients, and the metastatic ability of melanoma is regulated by IL-18 via vascular cell adhesion molecule-1 (Lissoni et al, 2000;Vidal-Vanaclocha et al, 2000). This suggests that the IL-18 derived from cancer cells is involved in the cancer metastatic process.…”

Section: Il-18 Is a Critical Mediator Of Vegf-enhanced Migrationmentioning

confidence: 99%

Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines

Kim

Song

et al. 2006

Oncogene

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Cell migration and angiogenesis are key steps in tumor metastasis. However, the mechanism of migration regulated by vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis, is not completely understood. This study examined the relationship between VEGF and migration, along with the mechanism involved in the VEGF-regulated migration of human gastric cancer cells. The level of cell migration was increased by recombinant human (rh)VEGF-165 in the VEGF receptor-2-expressing SNU-601 cells. Interleukin (IL)-18 is associated with the malignant progression of tumors. Accordingly, this study examined the effect of IL-18 on the migration of cancer cells in order to identify the factors involved in VEGF-enhanced migration. Inhibiting IL-18 markedly reduced the level of VEGF-enhanced migration, and IL-18 increased cell migration directly through filamentous-actin polymerization and tensin downregulation. It was confirmed that rhVEGF-165 increased IL-18 production significantly. An antioxidant and an extracellular signal-regulated kinase (ERK)1/2-specific inhibitor blocked rhVEGF-165-enhanced IL-18 production. Accordingly, rhVEGF-165 increased the generation of region of interest (ROI) and activated the ERK1/2 pathway. These results suggest that rhVEGF-165 enhances IL-18 production via the generation of ROI and ERK1/2 phosphorylation, which results in the increased migration of gastric cancer cells.

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IL-18 regulates IL-1β-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1

Cited by 315 publications

References 34 publications

Proangiogenic role of tumor-activated hepatic stellate cells in experimental melanoma metastasis

Proangiogenic role of tumor-activated hepatic stellate cells in experimental melanoma metastasis

C-reactive protein as a predictor of prognosis following curative resection for colorectal liver metastases

Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines

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