Abstract
The occurrence and development of liver cancer are essentially the most serious outcomes of uncontrolled liver regeneration. The progression of liver cancer is inevitably related to the abnormal microenvironment of liver regeneration. The deterioration observed in the microenvironment of liver regeneration is a necessary condition for the occurrence, development and metastasis of cancer. Therefore, the use of a technique to prevent and treat liver cancer via changes in the microenvironment of liver regeneration is a novel strategy. This strategy would be an effective way to delay, prevent or even reverse cancer occurrence, development and metastasis through an improvement in the liver regeneration microenvironment along with the integrated regulation of multiple components, targets, levels, channels and time sequences. In addition, the treatment of "tonifying Shen (Kidney) to regulate liver regeneration and repair by affecting stem cells and their microenvironment" can regulate "the dynamic imbalance between the normal liver regeneration and the abnormal liver regeneration"; this would improve the microenvironment of liver regeneration, which is also a mechanism by which liver cancer may be prevented or treated.
Similar content being viewed by others
References
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69–90.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108.
Chen JG, Zhang SW. Liver cancer epidemic in China: past, present and future. Sem Cancer Biol 2011;21:59–69.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893–2917.
Li HM. Regulatory network of nerve-endocrine-immune-liver regeneration. Chin J Integr Tradit West Med Liver Dis (Chin) 2014;24:193–196.
Choi SS, Diehl AM. Epithelial-to-mesenchymal transitions in the liver. Hepatology 2009;50:2007–2013.
Williams E, Iredale J. Hepatic regeneration and TGF-beta: growing to a prosperous perfection. Gut 2000;46:593–594.
Li HM. Regulation of liver regeneration: research progress and prospect. World Chin J Dig (Chin) 2015;23:3337–3343.
Zhou GY, Cai YP. Research progress of epithelial mesenchymal transition. J Zhengzhou Univ (Med Sci, Chin) 2010;45:353–355.
Lu HM, Ma LJ. Mechanism of epithelial mesenchymal transition and its role in tumor metastasis. Chin J Cancer Biother (Chin) 2009;16:541–545.
Nieto MA. Epithelial plasticity: a common theme in embryonic and cancer cells. Science 2013;342:1234850.
Katsuno Y, Lamouille S, Derynck R. TGF-β signaling and epithelial-mesenchymal transition in cancer progression. Curr Opin Oncol 2013;25:76–84.
Li HM. The unbalance of EMT/MET and "marrow cells cannot differentiate into liver cells". Chin J Integr Tradit West Med Liver Dis (Chin) 2012;21:385–389.
Okamoto K, Tajima H, Nakanuma S, Sakai S, Makino I, Kinoshita J, et al. Angiotensin II enhances epithelial-tomesenchymal transition through the interaction between activated hepatic stellate cells and the stromal cell-derived factor-1/CXCR4 axis in intrahepatic cholangiocarcinoma. Int J Oncol 2012;41:573–582.
Dooley S, Ten Dijke P. TGF-β in progression of liver disease. Cell Tissue Res 2012;347:245–256.
Wang YP, Yu GR, Lee MJ, Lee SY, Chu IS, Leem SH, et al. Lipocalin-2 negatively modulates the epithelialto-mesenchymal transition in liver cancer through the epidermal growth factor (TGF-beta1)/Lcn2/Twist1 pathway. Hepatology 2013;58:1349–1361.
**e G, Diehl AM. Evidence for and against epithelialto-mesenchymal transition in the liver. Am J Physiol Gastrointest Liver Physiol 2013;305:G881–G890.
van Zijl F, Zulehner G, Petz M, Schneller D, Kornauth C, Hau M, et al. Epithelial-mesenchymal transition in liver cancer. Future Oncol 2009;5:1169–1179.
Lu H, Liu J, Liu S, Zeng J, Ding D, Carstens RP, et al. Exo70 isoform switching upon epithelial-mesenchymal transition mediates cancer cell invasion. Dev Cell 2013;27:560–573.
Tam WL, Weinberg RA. The epigenetics of epithelialmesenchymal plasticity in cancer. Nat Med 2013;19:1438–1449.
Zhang W, Chen XP, Zhang WG, Zhang F, **ang S, Dong HH, et al. Hepatic non-parenchymal cells and extracellular matrix participate in oval cell-mediated liver regeneration. World J Gastroenterol 2009;15:552–560.
Suh SW, Lee KW, Lee JM, You T, Choi Y, Kim H, et al. Prediction of aggressiveness in early-stage liver cancer for selection of surgical resection. J Hepatol 2014;60:1219–1224.
Sun J, Jian ZX, Ou YL, Hou BH, Ou JR. The clinical value of postoperative prophylactic TACE on HCC patients with varied recurrent factors. J Pract Med (Chin) 2011;27:2148–2150.
Ding T, Xu J, Zhang Y, Guo RP, Wu WC, Zhang SD, et al. Endothelium-coated tumor clusters are associated with poor prognosis and micrometastasis of liver cancer after resection. Cancer 2011;117:4878–4889.
Zhong C, Wei W, Su XK, Li HD, Xu FB, Guo RP. Serum and tissue vascular endothelial growth factor predicts prognosis in liver cancer patients after partial liver resection. Hepatogastroenterology 2012;59:93–97.
Shi JH, Liu SZ, Wierød L, Scholz H, Anmarkrud JA, Huitfeldt HS, et al. RAF-targeted therapy for liver cancer in the regenerating liver. J Surg Oncol 2013;107:393–401.
Taub R. Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol 2004;5:836–847.
Huh CG, Factor VM, Sánchez A, Uchida K, Conner EA, Thorgeirsson SS. Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc Natl Acad Sci USA 2004;101:4477–4482.
Scarpino S, D'Alena FC, Di Napoli A, Ballarini F, Prat M, Ruco LP. Papillary carcinoma of the thyroid: evidence for a role for hepatocyte growth factor (HGF) in promoting tumour angiogenesis. J Pathol 2003;199:243–250.
Takeda S, Liu H, Sasagawa S, Dong Y, Trainor PA, Cheng EH, et al. HGF-MET signals via the MLL-ETS2 complex in liver cancer. J Clin Invest 2013;123:3154–3165.
Schoedel KE, Tyner VZ, Kim TH, Michalopoulos GK, Mars WM. HGF, MET, and matrix-related proteases in liver cancer, fibrolamellar variant, cirrhotic and normal liver. Mod Pathol 2003;16:14–21.
Giordano S, Columbano A. Met as a therapeutic target in HCC: facts and hopes. J Hepatol 2014;60:442–452.
Ozaki I, Mizuta T, Zhao G, Zhang H, Yoshimura T, Kawazoe S, et al. Induction of multiple matrix metalloproteinase genes in human liver cancer by hepatocyte growth factor via a transcription factor Ets-1. Hepatol Res 2003;27:289–301.
Koniaris LG, McKillop IH, Schwartz SI, Zimmers TA. Liver regeneration. J Am Coll Surg 2003;197:634–659.
Li HM. Fundamental and clinical application for liver disease treatment with therapeutic principle of "tonifying the Kidney to promote liver regeneration and repair". Mod Tradit Chin Med Mater Med World Sci Technol (Chin) 2013;15:1425–1428.
Li HM. Construction and application of tertiary prevention program for liver cancer based on "tonifying the Kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment". Chin J Integr Tradit West Med Liver Dis (Chin) 2015;25:369–372.
Li H, Zhang L. Liver regeneration microenvironment of hepatocellular carcinoma for prevention and therapy. Oncotarget 2017;8:1805–1813.
Li HM, Gao X, Yan XS. Studies of Zuogui Wan medicated serum pharmacology based on the co-culture system of bone marrow stem cells and hepatocytes. J Clin Rehabil Tissue Eng Res (Chin) 2010;14:3527–3532.
Chang MX, Wu MM, Li HM. Study on the inhibitory effect and mechanism of Curcumin combining with sorafenib on hepatoma HepG-2 cell. Chin J Integr Tradit West Med Liver Dis (Chin) 2016;26:277–280.
Li HM. Discussion on pathogenesis of mutual transformation between deficiency and cumulative pathological changes in liver cirrhosis. Chin Arch Tradit Chin Med (Chin) 2015;33:2825–2827.
Li HM, Gui WJ, Li JJ, Gao X, Yan XS, Cheng Y. Effects of Zuoguiwan on the liver regeneration related gene signaling pathway in female mice with male mice bone marrow transplant. J Clin Rehabil Tissue Eng Res (Chin) 2008;12:6069–6073.
Li HM, Gao X, Zhou MS. Effects of Zuogui Pill on gene expression profile of regenerate hepatic tissue in MSG-liver regeneration-rat. China J Tradit Chin Med Pharm (Chin) 2006;21:104–106.
Li HM, Yang ML, Mei JJ, Zhang LT, Qiu XF. The effects of Zuogui Pill on expression of TGF-α,β and its receptor in ARN and regenerative liver of the MSG-regeneration-rat. Chin J Hepatol (Chin) 2004;12:307–308.
Song HL, Li HM, Lin LS, Gao X, Zhao BB, Zhang J, et al. Effects of Diwu Yanggan Capsule on liver regeneration of rat with deficiency of Kidney essence and Liver blood. Chin J Integr Tradit West Med Liver Dis (Chin) 2013;23:90–92.
Li HM. Essence of deficiency syndrome and generate of vitality theory. Chin Arch Tradit Chin Med (Chin) 2011;29:2157–2160.
Li HM, Zhao BB, Gao X, Shen X, Wu Y, Zhang JR, et al. Tonifying Kidney network to modulate liver regeneration microenvironment to prevent and cure liver cancer. J Hubei Univ Tradit Chin Med (Chin) 2015;17:5–8.
Li HM. Microcirculation of liver cancer, microenvironment of liver regeneration, and the strategy of Chinese medicine. Chin J Integr Med 2016;22:163–167.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by the National Natural Science Foundation of China (No. 81373513), and Research Projects of Key Diseases of the National Traditional Chinese Medicine Clinical Research Center, Hubei Province (No. JDZX2012054, JDZX2015172)
Rights and permissions
About this article
Cite this article
Li, Hm., Ye, Zh. Microenvironment of liver regeneration in liver cancer. Chin. J. Integr. Med. 23, 555–560 (2017). https://doi.org/10.1007/s11655-017-2806-0
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11655-017-2806-0