Tumor microenvironment,medicine,Chinese traditional,Chinese medicine monomer,Chinese medicine compound,Research progress," /> Tumor microenvironment,medicine,Chinese traditional,Chinese medicine monomer,Chinese medicine compound,Research progress,"/> Progress in research on the effects of traditional Chinese medicine on the tumor microenvironment
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Journal of Integrative Medicine ›› 2017, Vol. 15 ›› Issue (4): 282-287.doi: 10.1016/S2095-4964(17)60345-5

Special Issue: Traditional Chinese Medicine

• Review • Previous Articles     Next Articles

Progress in research on the effects of traditional Chinese medicine on the tumor microenvironment

Wan-fu Lina, Jian-ying Lub, Bin-bin Chenga, Chang-quan Linga   

  1. a Changhai Hospital of Traditional Chinese Medicine, Second Military Medical University, Shanghai 200433, China
    b Department of Traditional Chinese Medicine, Jing’an Hospital of Integrated Traditional Chinese and Western Medicine, Hefei 200040, Anhui Province, China
  • Received:2017-01-06 Accepted:2017-04-05 Online:2017-07-15 Published:2018-12-19
  • Contact: Prof. Chang-quan Ling; E-mail: changquanling@smmu.edu.cn
  • Supported by:
    This study was supported by the National Natural Science Foundation of China (No. 81430101) and the Special Fund for the Development of Traditional Chinese Medicine in Anhui Province in 2015.

Tumor microenvironment (TME) has received more and more attention as modern medical research has begun to understand its importance in tumorigenesis. The occurrence, development, metastasis and drug resistance of tumors are closely related to TME. TME is a complicated system, including nontumor cells, their secreted cytokines, extracellular matrix, among other components. The concepts of wholism and multitarget regulation in traditional Chinese medicine (TCM) make it well suited to the regulation of TME. In this paper, the authors reviewed the progress of TME research and the effect of TCM on TME, providing some views of Chinese medicine in antitumor research.

Key words: Tumor microenvironment, medicine, Chinese traditional, Chinese medicine monomer, Chinese medicine compound, Research progress

1 Ma Y, Yang H, Pitt JM, Kroemer G, Zitvogel L.Therapyinduced microenvironmental changes in cancer.J Mol Med (Berl). 2016; 94(5): 497-508.
2 Paget S.The distribution of secondary growths in cancer of the breast. 1889.Cancer Metastasis Rev. 1989; 8(2): 98-101.
3 Mathot L, Stenninger J.Behavior of seeds and soil in the mechanism of metastasis: a deeper understanding.Cancer Sci. 2012; 103(4): 626-631.
4 Wang X, Wang N, Cheung F, Lao L, Li C, Feng Y.Chinese medicines for prevention and treatment of human hepatocellular carcinoma: current progress on pharmacological actions and mechanisms.J Integr Med. 2015; 13(3): 142-164.
5 Ling CQ, Yue XQ, Ling C.Three advantages of using traditional Chinese medicine to prevent and treat tumor.J Integr Med. 2014; 12(4): 331-335.
6 Egeblad M, Nakasone ES, Werb Z.Tumors as organs: complex tissues that interface with the entire organism. Dev Cell.2010; 18(6): 884-901.
7 Ruddle NH.High endothelial venules and lymphatic vessels in tertiary lymphoid organs: characteristics, functions, and regulation.Front Immunol. 2016; 7: 491.
8 Tammela T, Alitalo K.Lymphangiogenesis: molecular mechanisms and future promise.Cell. 2010; 140(4): 460-476.
9 Rhee I.Diverse macrophages polarization in tumor microenvironment.Arch Pharm Res. 2016; 39(11): 1588-1596.
10 Gordon S, Plüddemann A, Martinez Estrada F.Macrophage heterogeneity in tissues: phenotypic diversity and functions.Immunol Rev. 2014; 262(1): 36-55.
11 Cao W, Peters JH, Nieman D, Sharma M, Watson T, Yu J.Macrophage subtype predicts lymph node metastasis in oesophageal adenocarcinoma and promotes cancer cell invasionin vitro. Br J Cancer. 2015; 113(5): 738-746.
12 Chen DS, Mellman I.Oncology meets immunology: the cancer-immunity cycle.Immunity. 2013; 39(1): 1-10.
13 Gardner A, Ruffell B.Dendritic cells and cancer immunity.Trends Immunol. 2016; 37(12): 855-865.
14 Zong J, Keskinov AA, Shurin GV, Shurin MR.Tumorderived factors modulating dendritic cell function.Cancer Immunol Immunother. 2016; 65(7): 821-833.
15 Cekic C, Day YJ, Sag D, Linden J.Myeloid expression of adenosine A2A receptor suppresses T and NK cell responses in the solid tumor microenvironment.Cancer Res. 2014; 74(24): 7250-7259.
16 Sarhan D, Palma M, Mao Y, Adamson L, Kiessling R, Mellstedt H, Österborg A, Lundqvist A.Dendritic cell regulation of NK-cell responses involves lymphotoxin-α, IL-12, and TGF-β.Eur J Immunol. 2015; 45(6): 1783-1793.
17 Chaudhary B, Elkord E.Regulatory T cells in the tumor microenvironment and cancer progression: role and therapeutic targeting.Vaccines (Basel). 2016; 4(3): 28.
18 Otomo R, Otsubo C, Matsushima-Hibiya Y, Miyazaki M, Tashiro F, Ichikawa H, Kohno T, Ochiya T, Yokota J, Nakagama H, Taya Y, Enari M.TSPAN12 is a critical factor for cancer-fibroblast cell contact-mediated cancer invasion.Proc Natl Acad Sci U S A. 2014; 111(52): 18691-18696.
19 Dvorak HF.Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing.N Engl J Med. 1986; 315(26): 1650-1659.
20 Cuiffo BG, Karnoub AE.Mesenchymal stem cells in tumor development: emerging roles and concepts.Cell Adh Migr. 2012; 6(3): 220-230.
21 Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA.Mesenchymal stem cells within tumour stroma promote breast cancer metastasis.Nature. 2007; 449(7162): 557-563.
22 Au P, Tam J, Fukumura D, Jain RK.Bone marrow-derived mesenchymal stem cells facilitate engineering of longlasting functional vasculature.Blood. 2008; 111(9): 4551-4558.
23 Quante M, Tu SP, Tomita H, Gonda T, Wang SS, Takashi S, Baik GH, Shibata W, Diprete B, Betz KS, Friedman R, Varro A, Tycko B, Wang TC.Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth.Cancer Cell. 2011; 19(2): 257-272.
24 Paunescu V, Bojin FM, Tatu CA, Gavriliuc OI, Rosca A, Gruia AT, Tanasie G, Bunu C, Crisnic D, Gherghiceanu M, Tatu FR, Tatu CS, Vermesan S.Tumour-associated fibroblasts and mesenchymal stem cells: more similarities than differences.J Cell Mol Med. 2011; 15(3): 635-646.
25 Cocucci E, Meldolesi J.Ectosomes and exosomes: shedding the confusion between extracellular vesicles.Trends Cell Biol. 2015; 25(6): 364-372.
26 Mathivanan S, Ji H, Simpson RJ.Exosomes: extracellular organelles important in intercellular communication.J Proteomics. 2010; 73(10): 1907-1920.
27 Whiteside TL.Tumor-derived exosomes and their role in tumor-induced immune suppression.Vaccines (Basel). 2016; 4(4): 35.
28 Wang Z, Chen JQ, Liu JL, Tian L.Exosomes in tumor microenvironment: novel transporters and biomarkers.J Transl Med. 2016; 14(1): 297.
29 M’Boutchou MN, van Kempen LC. Analysis of the tumor microenvironment transcriptome via NanoString mRNA and miRNA expression profiling.Methods Mol Biol. 2016; 1458: 291-310.
30 Frediani JN, Fabbri M.Essential role of miRNAs in orchestrating the biology of the tumor microenvironment.Mol Cancer. 2016; 15(1): 42.
31 Böhme I, Bosserhoff AK.Acidic tumor microenvironment in human melanoma.Pigment Cell Melanoma Res. 2016; 29(5): 508-523.
32 Michiels C, Tellier C, Feron O.Cycling hypoxia: a key feature of the tumor microenvironment.Biochim Biophys Acta. 2016; 1866(1): 76-86.
33 Qian Q. Discussion on the treatment of cancer by traditional Chinese medicine. Zhejiang Zhong Xi Yi Jie He Za Zhi.2004; 14(6): 356-357. Chinese.
34 Zheng W, Yang JK. Tumor microenvironment and its TCM pathogenesis. Zhong Yi Za Zhi.2015; 56(20): 1720-1724. Chinese.
35 Owen S, Gao Y, Zhi X, Wei C, Wu Y, Jiang WG.Effect of Yangzheng Xiaoji extract, DME-25, on endothelial cells and their response to Avastin.Anticancer Res. 2016; 36(3): 1181-1192.
36 Min L, Ling W, Hua R, Qi H, Chen S, Wang H, Tang L, Shangguan W.Anti-angiogenic therapy for normalization of tumor vasculature: a potential effect of Buyang Huanwu decoction on nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential.Mol Med Rep. 2016; 13(3): 2518-2526.
37 Zhang EX, Zhou DH, Hou C. Effect of Yiqi Chutan Formula on antitumor immunity response through inhibiting production of tumor-associated macrophages. Zhonghua Zhong Liu Fang Zhi Za Zhi.2016; 23(10): 627-635. Chinese.
38 Luo Y, Wu J, Zhu X, Gong C, Yao C, Ni Z, Wang L, Ni L, Li Y, Zhu S.NK cell-dependent growth inhibition of Lewis lung cancer by Yu Ping Feng, an ancient Chinese herbal formula.Mediators Inflamm. 2016; 2016: 3541283.
39 Wang E, Bussom S, Chen J, Quinn C, Bedognetti D, Lam W, Guan F, Jiang Z, Mark Y, Zhao Y, Stroncek DF, White J, Marincola FM, Cheng YC.Interaction of a traditional Chinese medicine (PHY906) and CPT-11 on the inflammatory process in the tumor microenvironment.BMC Med Genomics. 2011; 4: 38.
40 Lam W, Jiang Z, Guan F, Huang X, Hu R, Wang J, Bussom S, Liu SH, Zhao H, Yen Y, Cheng YC.PHY906 (KD018), an adjuvant based on a 1800-year-old Chinese medicine, enhanced the anti-tumor activity of Sorafenib by changing the tumor microenvironment.Sci Rep. 2015; 5: 9384.
41 Liu J, Zhang J, Huang L, Zhu X, Chen W, Hu P.Xuefu Zhuyu Tang exerts antitumor effects by inhibiting glioma cell metastasis and invasion via regulating tumor microenvironment.Onco Targets Ther. 2016; 9: 3603-3612.
42 Xue YL, Meng XQ, Ma LJ, Yuan Z.Plumbagin exhibits an antiproliferative effect in human osteosarcoma cells by down-regulating FHL2 and interfering with Wnt/β-catenin signalling.Oncol Lett. 2016; 12(2): 1095-1100.
43 Su YC, Lin IH, Siao YM, Liu CJ, Yeh CC.Modulation of the tumor metastatic microenvironment and multiple signal pathways byPrunella vulgaris in human hepatocellular carcinoma. Am J Chin Med. 2016; 44(4): 835-849.
44 Wang N, Tan HY, Li L, Yuen MF, Feng Y.Berberine andCoptidis Rhizoma as potential anticancer agents: recent updates and future perspectives. J Ethnopharmacol. 2015; 176: 35-48.
45 Lin J, Li Q, Chen H, Lin H, Lai Z, Peng J.Hedyotis diffusa Willd. extract suppresses proliferation and induces apoptosis via IL-6-inducible STAT3 pathway inactivation in human colorectal cancer cells. Oncol Lett. 2015; 9(4): 1962-1970.
46 Zhou Z, Lu ZR. Molecular imaging of the tumor microenvironment. Adv Drug Deliv Rev.2016 Aug; Epub ahead of print.
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