Natural killer cells inhibit pulmonary metastasis of hepatocellular carcinoma
- Author:
- No author available
- Journal Title:
- World Chinese Journal of Digestology
- Issue:
- 22
- DOI:
- 10.11569/wcjd.v25.i22.2028
- Key Word:
- 自然杀伤细胞;侵袭;肝细胞肝癌;肺转移;白介素-2;Natural killer cells;Invasion;Hepatocellular carcinoma;Pulmonary metastasis;Interleukin-2
Abstract： AIM To investigate the inhibitory role of natural killer (NK) cells in liver cancer metastasis.METHODS NK cells were isolated from human peripheral blood mononuclear cells,cultivated and identified.In vitro,NK cells were used to suppress liver cancer cell proliferation,migration and metastasis.In vivo,the homing of NK cells in the liver of nude mice was detected.A nude mouse orthotopic liver transplantation model was used to assess the role of NK cells in inhibiting the growth and metastasis of liver cancer in vivo.The expression of NKG2D,NKB1,perforin and granular enzyme was detected to assess the stimulatory effect of interleukin (IL)-2 on NK cell immune function.RESULTS In vitro,NK cells inhibited the proliferation,migration and invasion of liver cancer cells.In vivo,NK cells could survive in the liver of nude mice for a long time.NK cells significantly inhibit the pulmonary metastasis of liver cancer in nude mice.However,the liver tumor growth was not inhibited by NK cells.IL-2 can strengthen the suppressor function of NK cells in tumors.CONCLUSION The immunological function of NK cells can be strengthened by IL-2 to inhibit liver cancer metastasis.
- [1]David Yiu-Kuen But,Ching-Lung Lai,Man-Fung Yuen.Natural history of hepatitis-related hepatocellular carcinoma[J].2008,(11).
- [2]朱玲燕,周嘉,刘彦章,等.自然杀伤细胞在原发性肝细胞肝癌中的浸润及其与预后的关系[J].2009,(11).
- [3]Sangiovanni, Angelo,Colombo, Massimo.Treatment of hepatocellular carcinoma: beyond international guidelines[J].2016,36(Suppl.1).
- [4].Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters[J].2009,9(1).
- [5]Akio, Uemura,Tetsuo, Takehara,Takuya, Miyagi,etc.Natural killer cell is a major producer of interferon gamma that is critical for the IL-12-induced anti-tumor effect in mice.[J].2010,59(3).
- [6]Qin,Y.,Zhu,X.-C.,Yang,X.,etc.MicroRNA-26a suppresses tumor growth and metastasis of human hepatocellular carcinoma by targeting interleukin-6-Stat3 pathway[J].2013,58(1).
- [7]Morisaki T,Nagamatsu I,Koya N,etc.Combinatorial cytotoxicity of gemcitabine and cytokine-activated killer cells in hepatocellular carcinoma via the NKG2D-MICA/B system.[J].2011,31(7).
- [8]Nomoto,M.,Takamura,M.,Matsuda,Y.,etc.Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with early recurrence[J].2012,56(2).
- [9]G. M. GERSUK,B. WESTERMARK,A. J. MOHABEER,etc.Inhibition of Human Natural Killer Cell Activity by Platelet-Derived Growth Factor (PDGF)[J].1991,33(5).
- [10]van der Slik AR,van Hall T,Verhoeven DH,etc.Evidence for natural killer cell-mediated protection from metastasis formation in uveal melanoma patients.[J].2009,50(6).
- [11]Wu,Y.,Kuang,D.-M.,Pan,W.-D.,etc.Monocyte/macrophage-elicited natural killer cell dysfunction in hepatocellular carcinoma is mediated by CD48/2B4 interactions[J].2013,57(3).
- [12]Bachanova V,Miller JS,Peterson KA,etc.Activated notch supports development of cytokine producing NK cells which are hyporesponsive and fail to acquire NK cell effector functions.[J].2009,15(2).
- [13]Xu,Z.,Chen,L.,Zhuang,R.,etc.MiR-30c-1* promotes natural killer cell cytotoxicity against human hepatoma cells by targeting the transcription factor HMBOX1[J].2012,103(4).
- [14]Hoechst B,Voigtlaender T,Ormandy L.Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor.[J].2009,50(3).
- [15]Meng J,Wang X,Zhang X,etc.T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates natural killer cell suppression in chronic hepatitis B.[J].2010,52(3).
- [16]Invernizzi, Federica,Vigano, Mauro,Grossi, Glenda,etc.The prognosis and management of inactive HBV carriers[J].2016,36(Suppl.1).
- [17]Ning Pan,Wei Jiang,Hang Sun,etc.KIR and HLA Loci Are Associated with Hepatocellular Carcinoma Development in Patients with Hepatitis B Virus Infection: A Case-Control Study.[J].2011,6(10).
- [18]Wang,G.,Chen,G.,Yang,Y.,etc.Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO[J].2012,318(2).
- [19]Mikuriya, Yoshihiro,Tashiro, Hirotaka,Kuroda, Shintaro,etc.Fatty liver creates a pro-metastatic microenvironment for hepatocellular carcinoma through activation of hepatic stellate cells[J].2015,136(4).
- [20]Park JH,Yoon JC,Lee JM,etc.Cell-to-cell contact with hepatitis C virus-infected cells reduces functional capacity of natural killer cells.[J].2011,85(23).
- [21]Hosui A,Takehara T,Tsunematsu H,etc.Fibroblast growth factor-2 enhances NK sensitivity of hepatocellular carcinoma cells.[J].2012,130(2).
- [22]Townsley, E.,O'Connor, G.,Cosgrove, C.,etc.Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells[J].2016,183(3).
- [23]Nishida,S.,Tanaka,Y.,Tryphonopoulos,P.,etc.Clinical-scale isolation of interleukin-2-stimulated liver natural killer cells for treatment of liver transplantation with hepatocellular carcinoma[J].2012,21(7).