Direct visualization of nitric oxide release by liver cells after the arrest of metastatic tumor cells in the hepatic microvasculature1

Qin, Ke; Qiu, Hongming; Rutherford, John D.; Yin, Zhao; Nance, Dwight M.; Orr, F. W.

doi:10.1016/j.jss.2003.09.008

Cited by 15 publications

(13 citation statements)

References 24 publications

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“…9,10 Our previous studies have demonstrated that the rate of apoptosis is significantly higher in the sinusoids compared to the TPV. This effect can be inhibited by using NO synthase inhibitor L-NAME, which indicates that the tumor cell apoptosis is associated with NO production.…”

Section: Discussionmentioning

confidence: 95%

“…12,13 The procedure was performed as described previously. 10 Briefly, after the liver perfusion was established, the perfusate was replaced by 4,5-diaminofluorescein. After an equilibration period of 45 minutes to allow uptake of 4,5-diaminofluorescein, the intravascular dye was removed by perfusion with dye-free medium for 5 minutes to reduce background.…”

Section: Methodsmentioning

confidence: 99%

“…10,12,13 After 15 minutes perfusion, the basal NO generation, expressed as the intensity of fluorescence signals in the periportal zone (zone 1) area, increased greater than 2-fold in both control groups. In comparison, there was less than one fold increase of fluorescence intensity in the cirrhosis model (P Ͻ .05).…”

Section: Measurement Of No Release By Confocal Microscopymentioning

confidence: 97%

“…8 Alternatively, tumor cell arrest in hepatic sinusoids can induce endothelial and hepatic NO release, causing tumor cell apoptosis and inhibiting metastasis. 9,10 We predicted these mechanisms would apply in a cirrhotic model. To examine this possibility, we established cirrhosis in C57BL/6 mice, using carbon tetrachloride (CCl 4 ) gastrogavage.…”

mentioning

confidence: 94%

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Impact of cirrhosis on the development of experimental hepatic metastases by B16F1 melanoma cells in C57BL/6 mice

et al. 2004

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Metastases rarely occur in human livers with cirrhosis in clinical studies. We postulated that this phenomenon would also occur in experimental cirrhosis. Cirrhosis was established in C57BL/6 mice by carbon tetrachloride (CCl 4 ) gastrogavage. B16F1 melanoma cells were injected into the mesenteric vein to induce hepatic metastases. Contrary to our postulate, there was greater than 4-fold increase in metastasis in animals with cirrhosis compared to controls. Intravital videomicroscopy showed that the hepatic sinusoids were narrower and more tumor cells were retained in the terminal portal vein ( T he liver is a common site of metastatic tumor growth. Interestingly, the liver with cirrhosis has been reported to inhibit metastasis. 1 In clinical studies, colorectal cancers rarely metastasize to livers with cirrhosis. 2,3 Autopsy studies have shown that the rate of metastasis to such livers is lower than that to normal livers. 4,5 However, the mechanisms responsible for this result are not clear. Vanbockrijck and Kloppel suggested that the lower incidence of metastasis is due to a shorter life expectancy of patients with cirrhosis. 6 Seymour and Charnley considered that venovenous shunting in cirrhosis may prevent tumor cells from reaching the liver, and that changes in the architecture of cirrhotic sinusoids may reduce metastasis. 5 The activation of Kupffer cells in cirrhosis may also inhibit the formation of hepatic metastases. 7 Based on previous studies, the fate of metastatic cells in the liver is determined by the expression of hepatic microvasculature adhesion molecules and the release of endothelial-derived nitric oxide (NO). Specifically, the expression of inducible vascular adhesion molecules can cause tumor cell arrest in terminal portal vein (TPV) and increase metastasis. 8 Alternatively, tumor cell arrest in hepatic sinusoids can induce endothelial and hepatic NO release, causing tumor cell apoptosis and inhibiting metastasis. 9,10 We predicted these mechanisms would apply in a cirrhotic model. To examine this possibility, we established cirrhosis in C57BL/6 mice, using carbon tetrachloride (CCl 4 ) gastrogavage. Liver metastasis was induced by injecting B16F1 melanoma cells into the portal venous system. Surprisingly, we found a significant increase in metastasis of B16F1 melanoma cells in animals with cirrhosis. Our studies demonstrated that alterations

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Section: Discussionmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Section: Measurement Of No Release By Confocal Microscopymentioning

confidence: 97%

mentioning

confidence: 94%

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Impact of cirrhosis on the development of experimental hepatic metastases by B16F1 melanoma cells in C57BL/6 mice

et al. 2004

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“…The main in-vivo biomechanical stimulus able to induce KLF2 expression is blood-derived shear stress, and interestingly it has been reported that shear stress upregulates the KLF2 target eNOS in the liver endothelium;15 27 therefore, we characterised the systemic and hepatic haemodynamics of all animals included in the present study. Animals with advanced cirrhosis, highly expressing KLF2, presented a marked increase in the quantity of blood flow entering the liver through the portal vein, thus favouring the expression of those endothelial genes upregulated by shear stress, including KLF2.…”

Section: Discussionmentioning

confidence: 99%

Endothelial expression of transcription factor Kruppel-like factor 2 and its vasoprotective target genes in the normal and cirrhotic rat liver

Gracia‐Sancho

Russo²,

García‐Calderó³

et al. 2010

Gut

131

108

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Role of the Host Inflammatory Response in Colon Carcinoma Initiation, Progression and Liver Metastasis

Brodt

2010

Metastasis of Colorectal Cancer

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Direct visualization of nitric oxide release by liver cells after the arrest of metastatic tumor cells in the hepatic microvasculature1

Cited by 15 publications

References 24 publications

Impact of cirrhosis on the development of experimental hepatic metastases by B16F1 melanoma cells in C57BL/6 mice

Impact of cirrhosis on the development of experimental hepatic metastases by B16F1 melanoma cells in C57BL/6 mice

Endothelial expression of transcription factor Kruppel-like factor 2 and its vasoprotective target genes in the normal and cirrhotic rat liver

Role of the Host Inflammatory Response in Colon Carcinoma Initiation, Progression and Liver Metastasis

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