Blockage of CXCR2 suppresses tumor growth of intrahepatic cholangiocellular carcinoma

Sueoka, Hideaki; Hirano, Toshio; Uda, Yugo; Iimuro, Yuji; Yamanaka, Junichi; Fujimoto, Jiro

doi:10.1016/j.surg.2013.12.037

Cited by 29 publications

(31 citation statements)

References 36 publications

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“…3b). These chemokines are reportedly key cytokines in the pathogenesis of CCA and its proliferative effect [20][21][22]. These data suggested the critical role of cholangiocyte senescence and the subsequent secretion of SASP components in the progression of biliary tract cancers associated with PBM and intrahepatic cholelithiasis.…”

Section: Discussionmentioning

confidence: 97%

Protective effect of phosphatidylcholine on lysophosphatidylcholine‐induced cellular senescence in cholangiocyte

Ohigashi

Kanno

Sugiyama

et al. 2019

J Hepato Biliary Pancreat

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Background Pancreaticobiliary maljunction and intrahepatic gallstones are at a high risk for biliary malignancy. Lysophosphatidylcholine (LPC) is increased in the bile of these patients, and we have previously reported that LPC‐induced cytotoxicity causes senescence‐associated secretory phenotype (SASP) in cholangiocytes. We aimed to determine the protective effect of phosphatidylcholine (PC) on LPC‐induced cholangiocyte cytotoxicity. Methods MMNK‐1, a human immortalized cholangiocyte cell line was treated with LPC with or without PC. To assess the biological effects of SASP components on cholangiocarcinoma, HuH28 and HuCCT1 (human cholangiocarcinoma cell lines) were cultured in the conditioned media where MMNK‐1 cells treated with LPC. Results The presence of PC reduced reactive oxygen species generation and oxidative DNA damage in MMNK‐1 treated with LPC. Moreover, SA‐β‐gal activity was markedly downregulated by PC. The secretion of SASP components, including interleukin (IL)‐8, IL‐6, and C‐C motif chemokine ligand 2 was also substantially reduced in the presence of PC. Cellular proliferation and migration were enhanced in HuCCT1 and HuH28 cells when cultured in the conditioned media, and these observations were suppressed by simultaneous addition of PC. Conclusion PC protects cholangiocytes against LPC‐induced cytotoxicity and cellular senescence, suggesting its potential as a target for inhibiting LPC‐related carcinogenesis and its promotion.

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Section: Discussionmentioning

confidence: 97%

Protective effect of phosphatidylcholine on lysophosphatidylcholine‐induced cellular senescence in cholangiocyte

Ohigashi

Kanno

Sugiyama

et al. 2019

J Hepato Biliary Pancreat

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“…). Interestingly, a previous report has demonstrated that blocking of CXC chemokine receptor 2, receptors for chemokines including CXCL8, CXCL1, CXCL2, and CXCL3 suppressed the development of cholangiocarcinoma .…”

Section: Discussionmentioning

confidence: 99%

Cholangiocyte senescence caused by lysophosphatidylcholine as a potential implication in carcinogenesis

Shimizu

Kanno

Sugiyama

et al. 2015

J Hepatobiliary Pancreat Sci

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“…Finally, a recently published study by Sueoka et al investigated the role of CXCR2 in promoting the development and growth of cholangiocarcinoma in vitro and in vivo. The authors showed that (i) blockage of CXCR2 using a knockdown strategy or a CXCR2 antagonist suppresses the growth of cholangiocarcinoma, (ii) CXCR2 is up-regulated in cholangiocarcinoma compared to adjacent liver tissue in human tissue resections, (iii) CXCR2 has a prognostic value in patients with intrahepatic cholangiocarcinoma (patients with high CXCR2 expression levels showed a poorer prognosis than patients with low CXCR2 levels), all suggesting that blocking CXCR2 may be a promising therapeutic approach for cholangiocarcinoma [36].…”

Section: Cholangiocarcinomamentioning

confidence: 99%

Role of chemokine pathways in hepatobiliary cancer

Ehling

Tacke

2016

Cancer Letters

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Blockage of CXCR2 suppresses tumor growth of intrahepatic cholangiocellular carcinoma

Cited by 29 publications

References 36 publications

Protective effect of phosphatidylcholine on lysophosphatidylcholine‐induced cellular senescence in cholangiocyte

Protective effect of phosphatidylcholine on lysophosphatidylcholine‐induced cellular senescence in cholangiocyte

Cholangiocyte senescence caused by lysophosphatidylcholine as a potential implication in carcinogenesis

Role of chemokine pathways in hepatobiliary cancer

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