Advertisement

Inhibitory effect of non-alcoholic steatohepatitis on colon cancer liver metastasis

Published:November 04, 2022DOI:https://doi.org/10.1016/j.ejso.2022.11.002

      Abstract

      Background

      The incidence of non-alcoholic steatohepatitis (NASH) is dramatically increasing, but the effect of NASH on colon cancer liver metastasis (CLM) is controversial. The aim of this study was to investigate the impact and mechanism of action of NASH on CLM using a western diet (WD)-fed mouse model.

      Methods

      Six-week-old male C57BL/6 J mice were used. They were divided into the WD group and control group with normal diet. MC38 colon cancer cells were injected into the spleen at 2, 6, 8 and 16 weeks, and mice were killed at 2 weeks after injection to evaluate hepatic steatosis, fibrosis, metastasis and mRNA/protein expression in the liver.

      Results

      Only mice fed a WD for 16 weeks showed hepatic fibrosis. These mice showed significantly higher alanine aminotransferase and total cholesterol levels compared with the control group (p < 0.05). The WD group showed significantly lower tumor number and smaller tumor diameter (p < 0.05). In the WD group, expression of SAA1, IL6, STAT3 and MMP9 mRNA in the liver was significantly lower than in the control group (p < 0.05). Serum amyloid A1 protein expression was also lower in the WD group.

      Conclusions

      The WD-fed NASH mouse model showed an inhibitory effect on CLM. Suppressed interleukin-6/signal transducer and activator of transcription 3 signaling and serum amyloid A/matrix metalloproteinase 9 expression may affect this phenomenon.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Surgical Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Jemal A.
        • Bray F.
        • Center M.M.
        • Ferlay J.
        • Ward E.
        • Forman D.
        Global cancer statistics.
        CA A Cancer J Clin. 2011; 61: 69-90
        • McMillan D.C.
        • McArdle C.S.
        Epidemiology of colorectal liver metastases.
        Surg Oncol. 2007; 16: 3-5
        • Gassmann P.
        • Haier J.
        The tumor cell-host organ interface in the early onset of metastatic organ colonisation.
        Clin Exp Metastasis. 2008; 25: 171-181
        • Younossi Z.M.
        • Koenig A.B.
        • Abdelatif D.
        • Fazel Y.
        • Henry L.
        • Wymer M.
        Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.
        Hepatology. 2016; 64: 73-84
        • Lv Y.
        • Zhang H.J.
        Effect of non-alcoholic fatty liver disease on the risk of synchronous liver metastasis: analysis of 451 consecutive patients of newly diagnosed colorectal cancer.
        Front Oncol. 2020; 10: 251
        • Kondo T.
        • Okabayashi K.
        • Hasegawa H.
        • Tsuruta M.
        • Shigeta K.
        • Kitagawa Y.
        The impact of hepatic fibrosis on the incidence of liver metastasis from colorectal cancer.
        Br J Cancer. 2016; 115: 34-39
        • Murono K.
        • Kitayama J.
        • Tsuno H.
        • Nozawa H.
        • Kawai K.
        • Sunami E.
        • et al.
        Hepatic steatosis is associated with lower incidence of liver metastasis from colorectal cancer.
        Int J Colorectal Dis. 2013; 28: 1065-1072
        • Hayashi S.
        • Masuda H.
        • Shigematsu M.
        Liver metastasis rare in colorectal cancer patients with fatty liver.
        Hepato-Gastroenterology. 1997; 44: 1069-1075
        • Nakamura M.
        • Suetsugu A.
        • Hasegawa K.
        • Matsumoto T.
        • Aoki H.
        • Kunisada T.
        • et al.
        Choline-deficientdiet-induced fatty liver is a metastasis-resistant microenvironment.
        Anticancer Res. 2017; 37: 3429-3434
        • Wen S.W.
        • Ager E.I.
        • Christophi C.
        Bimodal role of Kupffer cells during colorectal cancer liver metastasis.
        Cancer Biol Ther. 2013; 14: 606-613
        • Matsumura H.
        • Kondo T.
        • Ogawa K.
        • Tamura T.
        • Fukunaga K.
        • Murata S.
        • et al.
        Kupffer cells decrease metastasis of colon cancer cells to the liver in the early stage.
        Int J Oncol. 2014; 45: 2303-2310
        • Song E.
        • Chen J.
        • Ouyang N.
        • Wang M.
        • Exton M.S.
        • Heemann U.
        Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas-mediated apoptosis.
        Br J Cancer. 2001; 84: 1265-1271
        • Tamura R.
        • Masuda H.
        • Ishii Y.
        • Nemoto N.
        Relationship between fatty liver and liver metastasis in rats given injection of rat colon cancer cell line.
        Hepato-Gastroenterology. 1999; 46: 167-171
        • Masaki S.
        • Hashimoto Y.
        • Kunisho S.
        • Kimoto A.
        • Kitadai Y.
        Fatty change of the liver microenvironment influences the metastatic potential of colorectal cancer.
        Int J Exp Pathol. 2020; 101: 162-170
        • Machado M.V.
        • Michelotti G.A.
        • Xie G.
        • Almeida Pereira T.
        • Boursier J.
        • Bohnic B.
        • et al.
        Mouse models of diet-induced nonalcoholic steatohepatitis reproduce the heterogeneity of the human disease.
        PLoS One. 2015; 10e0127991
        • Lee J.W.
        • Stone M.L.
        • Porrett P.M.
        • Thomas S.K.
        • Komar C.A.
        • Li J.H.
        • et al.
        Hepatocytes direct the formation of a pro-metastatic niche in the liver.
        Nature. 2019; 567: 249-252
        • Uhlar C.M.
        • Burgess C.J.
        • Sharp P.M.
        • Whitehead A.S.
        Evolution of the serum amyloid A (SAA) protein superfamily.
        Genomics. 1994; 19: 228-235
        • Sander L.E.
        • Sackett S.D.
        • Dierssen U.
        • Beraza N.
        • Linke R.P.
        • Muller M.
        • et al.
        Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function.
        J Exp Med. 2010; 207: 1453-1464
        • Guo S.
        • Li J.
        • Huang Z.
        • Yue T.
        • Zhu J.
        • Wang X.
        • et al.
        The CBS-H 2 S axis promotes liver metastasis of colon cancer by upregulating VEGF through AP-1 activation.
        Br J Cancer. 2021; 126: 1055-1066
        • Pierre B.
        • FLIP Pathology Consortium
        Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease.
        Hepatology. 2014; 60: 565-575
        • Yada K.
        • Ishibashi H.
        • Mori H.
        • Morine Y.
        • Zhu C.
        • Feng R.
        • et al.
        The Kampo medicine“Daikenchuto (TU-100)” prevents bacterial translocation and hepatic fibrosis in a rat model of biliary atresia.
        Surgery. 2016; 159: 1600-1611
        • Tamura R.
        • Masuda H.
        • Ishii Y.
        • Nemoto N.
        Relationship between fatty liver and liver metastasis in rats given injection of rat colon cancer cell line.
        Hepato-Gastroenterology. 1999; 46: 167-171
        • Cheng L.
        • Geng L.
        • Dai B.
        • Zheng T.
        • Fu J.
        • Qiao L.
        • et al.
        Repression of let-7a cluster prevents adhesion of colorectal cancer cells by enforcing a mesenchymal phenotype in presence of liver inflammation.
        Cell Death Dis. 2018; 9: 489
        • Song E.
        • Ouyang J.C.
        • Wang M.
        • Exton M.S.
        • Heemann U.
        Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas-mediated apoptosis.
        Br J Cancer. 2001; 84: 1265-1271
        • Miller A.M.
        • Wang H.
        • Bertola A.
        • Park O.
        • Horiguchi N.
        • Ki S.H.
        • et al.
        Inflammation-associated interleukin-6/signal transducer and activator of transcription 3 activation ameliorates alcoholic and nonalcoholic fatty liver diseases in interleukin-10-deficient mice.
        Hepatology. 2011; 54: 846-856
        • Hou X.
        • Yin S.
        • Ren R.
        • Liu S.
        • Yong L.
        • Liu Y.
        • et al.
        Myeloid cell-specific IL-6 signaling promotes miR-223-enriched exosome production to attenuate NAFLD-associated fibrosis.
        Hepatology. 2021; 74: 116-132
        • Cai X.
        • Fang C.
        • Hayashi S.
        • Hao S.
        • Zhao M.
        • Tsutsui H.
        • et al.
        Pu-erh tea extract ameliorates high-fat diet-induced nonalcoholic steatohepatitis and insulin resistance by modulating hepatic IL-6/STAT3 signaling in mice.
        J Gastroenterol. 2016; 51: 819-829
        • Ye T.H.
        • Yang F.F.
        • Zhu Y.X.
        • Li Y.L.
        • Lei Q.
        • Song X.J.
        • et al.
        Inhibition of Stat3 signaling pathway by nifuroxazide improves antitumor immunity and impairs colorectal carcinoma metastasis.
        Cell Death Dis. 2017; 8: e2534
        • Li Z.
        • Hou Y.
        • Zhao M.
        • Li T.
        • Li Y.
        • Chang J.
        • et al.
        Serum amyloid a, a potential biomarker both in serum and tissue, correlates with ovarian cancer progression.
        J Ovarian Res. 2020; 13: 67
        • Cai B.
        • Liao K.
        • Song X.Q.
        • Wei W.Y.
        • Zhuang Y.
        • Zhang S.
        Patients with chronically diseased livers have lower incidence of colorectal liver metastases: a meta-analysis.
        PLoS One. 2014; 9e108618
        • Seymour K.
        • Charnley R.M.
        Evidence that metastasis is less common in cirrhotic than normal liver: a systematic review of post-mortem case-control studies.
        Br J Surg. 1999; 86: 1237-1242
        • Villeneuve J.P.
        The natural history of chronic hepatitis B virus infection.
        J Clin Virol. 2005; 34: S139-S142
        • Tordjmann T.
        • Soulie A.
        • Guettier C.
        • Schmidt M.
        • Berthou C.
        • et al.
        Perforin and granzyme B lytic protein expression during chronic viral and autoimmune hepatitis.
        Liver. 1998; 18: 391-397
        • Karube H.
        • Masuda H.
        • Hayashi S.
        • Ishii Y.
        • Nemoto N.
        Fatty liver suppressed the angiogenesis in liver metastatic lesions.
        Hepato-Gastroenterology. 2000; 47: 1541-1545
        • Otto C.
        • Kaemmerer U.
        • Illert B.
        • Muehling B.
        • Pfetzer N.
        • et al.
        Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides.
        BMC Cancer. 2008; 8: 122-133