Splenectomy suppresses growth and metastasis of hepatocellular carcinoma through decreasing myeloid-derived suppressor cells in vivo

Xin Long , Jian Wang , Jian-ping Zhao , Hui-fang Liang , Peng Zhu , Qi Cheng , Qian Chen , Yan-hui Wu , Zhan-guo Zhang , Bi-xiang Zhang , Xiao-ping Chen

Current Medical Science ›› 2016, Vol. 36 ›› Issue (5) : 667 -676.

PDF
Current Medical Science ›› 2016, Vol. 36 ›› Issue (5) : 667 -676. DOI: 10.1007/s11596-016-1643-2
Article

Splenectomy suppresses growth and metastasis of hepatocellular carcinoma through decreasing myeloid-derived suppressor cells in vivo

Author information +
History +
PDF

Abstract

The function of the spleen in tumor development has been investigated for years. The relationship of the spleen with hepatocellular carcinoma (HCC), a huge health burden worldwide, however, remains unknown. The present study aimed to examine the effect of splenectomy on the development of HCC and the possible mechanism. Mouse hepatic carcinoma lines H22 and Hepa1-6 as well as BALB/c and C57 mice were used to establish orthotopic and metastatic mouse models of liver cancer. Mice were divided into four groups, including control group, splenectomy control group (S group), tumor group (T group) and tumor plus splenectomy group (T+S group). Tumor growth, metastases and overall survival were assessed at determined time points. Meanwhile, myeloid-derived suppressor cells (MDSCs) were isolated from the peripheral blood (PB), the spleen and liver tumors, and then measured by flow cytometery. It was found that liver cancer led to splenomegaly, and increased the percentage of MDSCs in the PB and spleen in the mouse models. Splenectomy inhibited the growth and progression of liver cancer and prolonged the overall survival time of orthotopic and metastatic models, which was accompanied by decreased proportion of MDSCs in the PB and tumors of liver cancer-bearing mouse. It was suggested that splenectomy could be considered an adjuvant therapy to treat liver cancer.

Keywords

splenectomy / liver cancer / myeloid-derived suppressor cells / adjuvant therapy

Cite this article

Download citation ▾
Xin Long, Jian Wang, Jian-ping Zhao, Hui-fang Liang, Peng Zhu, Qi Cheng, Qian Chen, Yan-hui Wu, Zhan-guo Zhang, Bi-xiang Zhang, Xiao-ping Chen. Splenectomy suppresses growth and metastasis of hepatocellular carcinoma through decreasing myeloid-derived suppressor cells in vivo. Current Medical Science, 2016, 36(5): 667-676 DOI:10.1007/s11596-016-1643-2

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

FornerA, LlovetJM, BruixJ. Hepatocellular carcinoma. Lancet, 2012, 379(9822): 1245-1255 PMID: 22353262

[2]

YongKJ, GaoC, LimJS, et al. . Oncofetal gene SALL4 in aggressive hepatocellular carcinoma. N Engl J Med, 2013, 368(24): 2266-2276 PMID: 23758232 PMCID: 3781214

[3]

FloresA, MarreroJA. Emerging trends in hepatocellular carcinoma: focus on diagnosis and therapeutics. Clin Med Insights Oncol, 2014, 8: 71-76 PMID: 24899827 PMCID: 4039215

[4]

WeiKR, YuX, ZhengRS, et al. . Incidence and mortality of liver cancer in China, 2010. Chin J Cancer, 2014, 33(8): 388-394 PMID: 25104174 PMCID: 4135368

[5]

Wei S, Hao X, Zhan D, et al. Are surgical indications of Barcelona Clinic Liver Cancer staging classification justified? J Huazhong Univ Sci Technolog Med Sci, 2011,31(5):637–641

[6]

WeiS, XiongM, ZhanDQ, et al. . Ku80 functions as a tumor suppressor in hepatocellular carcinoma by inducing S-phase arrest through a p53-dependent pathway. Carcinogenesis, 2012, 33(3): 538-547 PMID: 22226916

[7]

ColovaiAI, GiatzikisC, HoEK, et al. . Flow cytometric analysis of normal and reactive spleen. Mod Pathol, 2004, 17(8): 918-927 PMID: 15263909

[8]

MebiusRE, KraalG. Structure and function of the spleen. Nat Rev Immunol, 2005, 5(8): 606-616 PMID: 16056254

[9]

Dieguez-AcunaFJ, GygiSP, DavisM, et al. . Splenectomy: a new treatment option for ALL tumors expressing Hox-11 and a means to test the stem cell hypothesis of cancer in humans. Leukemia, 2007, 21(10): 2192-2194 PMID: 17713543

[10]

Cortez-RetamozoV, EtzrodtM, NewtonA, et al. . Origins of tumor-associated macrophages and neutrophils. Proc Natl Acad Sci USA, 2012, 109(7): 2491-2496 PMID: 22308361 PMCID: 3289379

[11]

UgelS, PeranzoniE, DesantisG, et al. . Immune tolerance to tumor antigens occurs in a specialized environment of the spleen. Cell Rep, 2012, 2(3): 628-639 PMID: 22959433

[12]

XiaS, LiX, ChengL, et al. . Chronic intake of high fish oil diet induces myeloid-derived suppressor cells to promote tumor growth. Cancer Immunol Immunother, 2014, 63(7): 663-673 PMID: 24691944 PMCID: 4246012

[13]

ShakedY, CerviD, NeumanM, et al. . The splenic microenvironment is a source of proangiogenesis/inflammatory mediators accelerating the expansion of murine erythroleukemic cells. Blood, 2005, 105(11): 4500-4507 PMID: 15701719 PMCID: 1895028

[14]

PrehnRT. The paradoxical effects of splenectomy on tumor growth. Theor Biol Med Model, 2006, 3: 23 PMID: 16800890 PMCID: 1538594

[15]

SonodaK, IzumiK, MatsuiY, et al. . Decreased growth rate of lung metastatic lesions after splenectomy in mice. Eur Surg Res, 2006, 38(5): 469-475 PMID: 16940732

[16]

HanahanD, WeinbergRA. Hallmarks of cancer: the next generation. Cell, 2011, 144(5): 646-674 PMID: 21376230

[17]

GabrilovichDI, NagarajS. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol, 2009, 9(3): 162-174 PMID: 19197294 PMCID: 2828349

[18]

DamuzzoV, PintonL, DesantisG, et al. . Complexity and challenges in defining myeloid-derived suppressor cells. Cytometry B Clin Cytom, 2015, 88(2): 77-91 PMID: 25504825

[19]

ChiN, TanZ, MaK, et al. . Increased circulating myeloid-derived suppressor cells correlate with cancer stages, interleukin-8 and -6 in prostate cancer. Int J Clin Exp Med, 2014, 7(10): 3181-3192 PMID: 25419348 PMCID: 4238489

[20]

LiRJ, LiuL, GaoW, et al. . Cyclooxygenase-2 blockade inhibits accumulation and function of myeloid-derived suppressor cells and restores T cell response after traumatic stress. J Huazhong Univ Sci Technolog Med Sci, 2014, 34(2): 234-240 PMID: 24710938

[21]

ZhuXJ, HuJ, SunL, et al. . Amplification of functional myeloid-derived suppressor cells during stem cell mobilization induced by granulocyte colony-stimulationfactor. J Huazhong Univ Sci Technolog Med Sci, 2013, 33(6): 817-821 PMID: 24337841

[22]

SchmidM, ZimaraN, WegeAK, et al. . Myeloid-derived suppressor cell functionality and interaction with Leishmania major parasites differ in C57BL/6 and BALB/c mice. Eur J Immunol, 2014, 44(11): 3295-3306 PMID: 25142017

[23]

MovahediK, GuilliamsM, Van den BosscheJ, et al. . Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cellsuppressive activity. Blood, 2008, 111(8): 4233-4244 PMID: 18272812

[24]

YounJI, NagarajS, CollazoM, et al. . Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol, 2008, 181(8): 5791-5802 PMID: 18832739 PMCID: 2575748

[25]

CondamineT, RamachandranI, YounJI, et al. . Regulation of tumor metastasis by myeloid-derived suppressor cells. Annu Rev Med, 2015, 66: 97-110 PMID: 25341012

[26]

YounJI, CollazoM, ShalovaIN, et al. . Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. J Leukoc Biol, 2012, 91(1): 167-181 PMID: 21954284 PMCID: 3250305

[27]

MurdocC, MuthanaM, CoffeltSB, et al. . The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer, 2008, 8(8): 618-631

[28]

SkabytskaY, WolbingF, GuntherC, et al. . Cutaneous innate immune sensing of toll-like receptor 2-6 ligands suppresses T cell immunity by inducing myeloid-derived suppressor cells. Immunity, 2014, 41(5): 762-775 PMID: 25456159

[29]

Diaz-MonteroCM, SalemML, NishimuraMI, et al. . Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother, 2009, 58(1): 49-59 PMID: 18446337

[30]

RenM, YeL, HaoX, et al. . Polysaccharides from Tricholoma matsutake and Lentinus edodes enhance 5-fluorouracil-mediated H22 cell growth inhibition. J Tradit Chin Med, 2014, 34(3): 309-316 PMID: 24992758

[31]

LiP, FengZ, ZhangG, et al. . Inhibitory effect of recombinant endostatin on angiogenesis and tumor growth of hepatoma. J Huazhong Univ Sci Technolog Med Sci, 2003, 23(3): 223-226 PMID: 14526417

[32]

QinL, WangX, DuanQ, et al. . Inhibitory effect of melatonin on the growth of H22 hepatocarcinoma cells by inducing apoptosis. J Huazhong Univ Sci Technolog Med Sci, 2004, 24(1): 19-21 PMID: 15165106

[33]

ZhangB, HalderSK, ZhangS, et al. . Targeting transforming growth factor-beta signaling in liver metastasis of colon cancer. Cancer Lett, 2009, 277(1): 114-120 PMID: 19147275 PMCID: 2776056

[34]

DingZY, JinGN, WangW, et al. . Reduced expression of transcriptional intermediary factor 1 gamma promotes metastasis and indicates poor prognosis of hepatocellular carcinoma. Hepatology, 2014, 60(5): 1620-1636 PMID: 24954480

[35]

SchwarzRE, HiserodtJC. Effects of splenectomy on the development of tumor-specific immunity. J Surg Res, 1990, 48(5): 448-453 PMID: 2352420

[36]

BrooksSP, RichGA, HuhYS, et al. . Lymphoid cell populations in splenectomized and nonsplenectomized SJL/J mice bearing Hodgkin’s disease-like reticulum cell sarcoma. J Pediatr Surg, 1986, 21(12): 1114-1118 PMID: 2947988

[37]

MiwaH, KojimaK, KobayashiT, et al. . The tumor—immunological significance of splenectomy for cancer therapy. Nihon Geka Gakkai Zasshi, 1983, 84(9): 970-973 PMID: 6427598

[38]

Jing-ShiW, Yi-NiW, LinW, et al. . Splenectomy as a treatment for adults with relapsed hemophagocytic lymphohistiocytosis of unknown cause. Ann Hematol, 2015, 94(5): 753-760 PMID: 25512183

[39]

DerlatkaP, Grabowska-DerlatkaL, SienkoJ, et al. . Splenectomy as a part of debulking surgery in patients with advanced ovarian cancer. Ginekol Pol, 2014, 85(8): 605-608 PMID: 25219141

[40]

SantosFP, TamCS, KantarjianH, et al. . Splenectomy in patients with myeloproliferative neoplasms: efficacy, complications and impact on survival and transformation. Leuk Lymphoma, 2014, 55(1): 121-127 PMID: 23573823

[41]

ChenXP, WuZD, HuangZY, et al. . Use of hepatectomy and splenectomy to treat hepatocellular carcinoma with cirrhotic hypersplenism. Br J Surg, 2005, 92(3): 334-339 PMID: 15672441

[42]

SolitoS, MarigoI, PintonL, et al. . Myeloid-derived suppressor cell heterogeneity in human cancers. Ann N Y Acad Sci, 2014, 1319: 47-65 PMID: 24965257

[43]

HochstB, SchildbergFA, SauerbornP, et al. . Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion. J Hepatol, 2013, 59(3): 528-535 PMID: 23665041

AI Summary AI Mindmap
PDF

101

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/