Evidence that metastasis is less common in cirrhotic than normal liver: a systematic review of post-mortem case–control studies

Seymour, Keith; Charnley, RM

doi:10.1046/j.1365-2168.1999.01228.x

Cited by 54 publications

(54 citation statements)

References 23 publications

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“…Our results support previous clinical data, and confirm that cirrhotic livers are not a favourable environment for metastatic tumour cells (Seymour and Charnley, 1999). More interestingly, treatment of colon cancer cells with Kupffer cellconditioned media from cirrhotic livers dramatically reduced the occurrence of metastases in normal rat livers to the extent that was comparable to metastases in cirrhotic livers.…”

Section: Discussionsupporting

confidence: 91%

“…Metastases of colorectal cancers into injured livers, such as chronic viral hepatitis (Utsunimoiya et al, 1999), liver cirrhosis (Seymour and Charnley, 1999) and fatty liver (Hayashi et al, 1997), are rare, with an incidence ranging from 0-8%. Recent studies suggest that in these hepatic disorders, changes in liverassociated immunity may play an important role in hindering hepatic metastasis formation.…”

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confidence: 99%

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Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas-mediated apoptosis

et al. 2001

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Summary Metastasis of colorectal carcinomas rarely occurs in cirrhotic livers. Our study investigated the influence of activated Kupffer cells from cirrhotic rat livers on hepatic colonization and FasR-mediated apoptosis of colon cancer cells. A rat colon cancer cell line, RCN-9, was used to inoculate rat livers. Treatment with conditioned media of Kupffer cells isolated from CCl 4 -induced cirrhotic rat livers (cirrhotic KCM) significantly reduced the incidence of hepatic colonization of RCN-9 cells. In vitro cytotoxicity of Kupffer cells and tumour infiltrating lymphocytes (TILs) on RCN-9 cells was evaluated using [ 3 H]-release assay. RCN-9 cells were resistant to cytotoxicity mediated by cirrhotic Kupffer cells, but were sensitized to TIL-mediated killing after treatment with cirrhotic KCM. The specific killing induced by TILs was FasR-mediated, as it was inhibited by ZB4, an antagonistic anti-FasR antibody. In agreement, cirrhotic KCM increased recombinant Fas ligand-induced apoptosis of RCN-9 cells, and up-regulated FasR expression on RCN-9 cells as evaluated by RT-PCR and flow cytometry. These findings suggest that Kupffer cells in cirrhotic livers sensitize metastatic colon cancer cells to FasR-mediated apoptosis by up-regulating the receptors, which thus prepare them to be eliminated by infiltrating lymphocytes.

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Section: Discussionsupporting

confidence: 91%

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confidence: 99%

Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas-mediated apoptosis

et al. 2001

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“…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.…”

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confidence: 90%

“…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).…”

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confidence: 99%

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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“…Hepatocyte-derived ECM, in particular heparin proteoglycan, stimulates the proliferation of colon cancer cell lines via induction of autocrine growth factors and their receptors [6]. Additionnaly, the fact that cirrhosis may inhibit metastasis formation supports the view that the pathological background of the host liver also influences its colonization by colon cancer cells [51,52].…”

Section: Microenvironmental Control Of Hepatic Metastasis Genes In Comentioning

confidence: 57%

Recent Advances in Colorectal Cancer Research: The Microenvironment Impact

Houle

Huot

2011

Cancer Microenvironment

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Evidence that metastasis is less common in cirrhotic than normal liver: a systematic review of post-mortem case–control studies

Cited by 54 publications

References 23 publications

Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas-mediated apoptosis

Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas-mediated apoptosis

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

Recent Advances in Colorectal Cancer Research: The Microenvironment Impact

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