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

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Ke QiF W Orr

Abstract

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 (TPV) in cirrhotic livers. Immunohistochemistry demonstrated that the expression of vascular adhesion molecules was significantly increased in cirrhosis. Using confocal microscopy and the fluorescent nitric oxide (NO) probe 4,5-diaminofluorescein diacetate, a significantly lower level of NO release was detected in livers with cirrhosis both in basal conditions and after tumor cell arrest. Eight hours after mesenteric vein tumor cell injection, the percentage of apoptotic tumor cells in the sinusoids was 17% +/- 2% in livers with cirrhosis and 30% +/- 5% in normal livers. More mitotic and Ki-67 labeled tumor cells were seen in livers with c...Continue Reading

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Citations

Aug 27, 2011·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Fernando Vidal-Vanaclocha
Nov 12, 2013·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Dongwei Gao, Sha Li
Dec 18, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alphonse E SiricaJennifer L Dewitt
Jun 30, 2011·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Emilie DahlLise L Gluud
Nov 23, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yoshitaka KimuraTadatsugu Taniguchi
Jun 12, 2020·Seminars in Cancer Biology·Aaron T CinerPnina Brodt

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