TGF-β与IL-6对胃癌发展和转移的影响
Effects of TGF-β and IL-6 on the Development and Metastasis of Gastric Cancer
DOI: 10.12677/MD.2022.121011, PDF,   
作者: 王英健, 徐 剑*:佳木斯大学附属第一医院,黑龙江 佳木斯
关键词: 胃癌TGF-βIL-6腹膜转移Gastric Cancer TGF-β IL-6 Peritoneal Metastasis
摘要: 胃癌是人类消化系统中最常见的恶性肿瘤,而胃癌的发展与转移是一个十分复杂的过程,多个因素参与其中。TGF-β作为一类多功能的细胞因子,通过促进上皮–间质转化、血管生成、免疫逃避等途径,在胃癌的发展与转移中起到了关键性的作用。IL-6则是一类炎性因子,通过与其受体结合进而激活相关信号转导通路、参与细胞的上皮–间质转化、介导免疫系统等影响了胃癌发展和转移。
Abstract: Gastric cancer is the most common malignant tumor in human digestive system, and the development and metastasis of gastric cancer are a very complex process, in which many factors are in-volved. TGF-β as a kind of multifunctional cytokines, they play a key role in the development and metastasis of gastric cancer by promoting epithelial mesenchymal transformation, angiogenesis and immune escape. IL-6 is a kind of inflammatory factor, which affects the development and me-tastasis of gastric cancer by binding to its receptor, activating related signal transduction pathways, participating in cell epithelial mesenchymal transformation and mediating immune system.
文章引用:王英健, 徐剑. TGF-β与IL-6对胃癌发展和转移的影响[J]. 医学诊断, 2022, 12(1): 65-71. https://doi.org/10.12677/MD.2022.121011

参考文献

[1] Ferlay, J., Colombet, M., Soerjomataram, I., et al. (2019) Estimating the Global Cancer Incidence and Mortality in 2018: GLOBOCAN Sources and Methods. International Journal of Cancer, 144, 1941-1953. [Google Scholar] [CrossRef] [PubMed]
[2] Chen, W., Zheng, R., Baade, P.D., et al. (2016) Cancer Statistics in China, 2015. CA: A Cancer Journal for Clinicians, 66, 115-132. [Google Scholar] [CrossRef] [PubMed]
[3] Bray, F., Ferlay, J., Soerjomataram, I., et al. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424. [Google Scholar] [CrossRef] [PubMed]
[4] Maeda, H., Kobayashi, M. and Sakamoto, J. (2015) Evaluation and Treatment of Malignant Ascites Secondary to Gastric Cancer. World Journal of Gastroenterology, 21, 10936-10947. [Google Scholar] [CrossRef] [PubMed]
[5] Thomassen, I., van Gestel, Y.R., van Ramshorst, B., et al. (2014) Peritoneal Carcinomatosis of Gastric Origin: A Population-Based Study on Incidence, Survival and Risk Factors. International Journal of Cancer, 134, 622-628. [Google Scholar] [CrossRef] [PubMed]
[6] Yamamoto, M., Baba, H., Kakeji, Y., et al. (2004) Prognostic Significance of Tumor Markers in Peritoneal Lavage in Advanced Gastric Cancer. Oncology, 67, 19-26. [Google Scholar] [CrossRef] [PubMed]
[7] Paget, S. (1989) Distribution of Secondary Growths in Cancer of the Breast. Cancer and Metastasis Reviews, 8, 98-101.
[8] 那迪. 胃癌细胞对腹膜间皮细胞损伤的研究[D]: [博士学位论文]. 沈阳: 中国医科大学, 2010.
[9] Tsukada, T., Fushida, S., Harada, S., Yagi, Y., Kinoshita, J., Oyama, K., Tajima, H., Fujita, H., Ninomiya, I., Fujimura, T. and Ohta, T. (2012) The Role of Human Peritoneal Mesothelial Cells in the Fibrosis and Progression of Gastric Cancer. International Journal of Oncology, 41, 476-482. [Google Scholar] [CrossRef] [PubMed]
[10] Katz, L.H., Likhter, M., Jogunoori, W., Belkin, M., Ohshiro, K. and Mishra, L. (2016) TGF-β Signaling in Liver and Gastrointestinal Cancers. Cancer Letters, 379, 166-172. [Google Scholar] [CrossRef] [PubMed]
[11] Moses, H.L., Roberts, A.B. and Derynck, R. (2016) The Discovery and Early Days of TGF-β: A Historical Perspective. Cold Spring Harbor Perspectives in Biology, 8, a021865. [Google Scholar] [CrossRef] [PubMed]
[12] Miyazawa, K. and Miyazono, K. (2017) Regulation of TGF-Beta Family Signaling by Inhibitory Smads. Cold Spring Harbor Perspectives in Biology, 9, a022095. [Google Scholar] [CrossRef] [PubMed]
[13] Fabregat, I., Fernando, J., Mainez, J. and Sancho, P. (2014) TGF-Beta Signaling in Cancer Treatment. Current Pharmaceutical Design, 20, 2934-2947. [Google Scholar] [CrossRef] [PubMed]
[14] Lv, Z.D., Zhao, W.J., Jin, L.Y., et al. (2017) Blocking TGF-β1 by P17 Peptides Attenuates Gastric Cancer Cell Induced Peritoneal Fibrosis and Prevents Peritoneal Dissemination in Vitro and in Vivo. Biomedicine & Pharmacotherapy, 88, 27-33. [Google Scholar] [CrossRef] [PubMed]
[15] Hu, W.Q., et al. (2014) High Expression of Transform Growth Factor Beta 1 in Gastric Cancer Confers Worse Outcome: Results of a Cohort Study on 184 Patients. Hepatogastroenterology, 61, 245-250.
[16] Dongre, A. and Weinberg, R.A. (2019) New Insights into the Mechanisms of Epithelial-Mesenchymal Transition and Implications for Cancer. Nature Reviews Molecular Cell Biology, 20, 69-84. [Google Scholar] [CrossRef] [PubMed]
[17] Lamouille, S., Xu, J. and Derynck, R. (2014) Molecular Mechanisms of Epithelial-Mesenchymal Transition. Nature Reviews Molecular Cell Biology, 15, 178-196. [Google Scholar] [CrossRef] [PubMed]
[18] Jung, H.Y., Fattet, L. and Yang, J. (2015) Molecular Pathways: Linking Tumor Microenvironment to Epithelial-Mesenchymal Transition in Metastasis. Clinical Cancer Research, 21, 962-968. [Google Scholar] [CrossRef
[19] Mittal, V. (2018) Epithelial Mesenchymal Transition in Tumor Metastasis. Annual Review of Pathology: Mechanisms of Disease, 13, 395-412. [Google Scholar] [CrossRef] [PubMed]
[20] Morikawa, M., Derynck, R. and Miyazono, K. (2016) TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology. Cold Spring Harbor Perspec-tives in Biology, 8, a021873. [Google Scholar] [CrossRef] [PubMed]
[21] Gonzalez, D.M. and Medici, D. (2014) Signaling Mechanisms of the Epithelial-Mesenchymal Transition. Science Signaling, 7, re8. [Google Scholar] [CrossRef] [PubMed]
[22] Zavadil, J., Bitzer, M., Liang, D., Yang, Y.C., Massimi, A., Kneitz, S., Piek, E. and Bottinger, E.P. (2001) Genetic Programs of Epithelial Cell Plasticity Directed by Transforming Growth Factor-β. Proceedings of the National Academy of Sciences of the United States of America, 98, 6686-6691. [Google Scholar] [CrossRef] [PubMed]
[23] Lee, M.K., Pardoux, C., Hall, M.C., Lee, P.S., Warburton, D., Qing, J., Smith, S.M. and Derynck, R. (2007) TGF-β Activates Erk MAP Kinase Signalling through Direct Phosphorylation of ShcA. The EMBO Journal, 26, 3957-3967. [Google Scholar] [CrossRef] [PubMed]
[24] Vo, B.T., Morton, D., Komaragiri, S., Millena, A.C., Leath, C. and Khan, S.A. (2013) TGF-β Effects on Prostate Cancer Cell Migration and Invasion Are Mediated by PGE2 through Activation of PI3K/AKT/mTOR Pathway. Endocrinology, 154, 1768-1779. [Google Scholar] [CrossRef] [PubMed]
[25] Carmeliet, P. and Jain, R.K. (2000) Angiogenesis in Cancer and Other Diseases. Nature, 407, 249-257. [Google Scholar] [CrossRef] [PubMed]
[26] Goumans, M.J., Valdimarsdottir, G., Itoh, S., Rosendahl, A., Sideras, P. and Dijke, P.T. (2002) Balancing the Activation State of the Endothelium via Two Distinct TGF-β Type I Receptors. The EMBO Journal, 21, 1743-1753. [Google Scholar] [CrossRef] [PubMed]
[27] David, C.J. and Massague, J. (2018) Contextual Determinants of TGF-β Action in Development, Immunity and Cancer. Nature Reviews Molecular Cell Biology, 19, 419-435. [Google Scholar] [CrossRef] [PubMed]
[28] Calon, A., Espinet, E., Palomo-Ponce, S., Tauriello, D.V.F., Iglesias, M., Céspedes, M.V., Sevillano, M., Nadal, C., Jung, P., Zhang, X.H.F., et al. (2012) Dependency of Colorectal Cancer on a TGF-β-Driven Program in Stromal Cells for Metastasis Initiation. Cancer Cell, 22, 571-584. [Google Scholar] [CrossRef] [PubMed]
[29] Li, M.O., Wan, Y.Y., Sanjabi, S., Robertson, A.K. and Flavell, R.A. (2006) Transforming Growth Factor-Beta Regulation of Immune Responses. Annual Review of Immunology, 24, 99-146. [Google Scholar] [CrossRef] [PubMed]
[30] Vivier, E., Tomasello, E., Baratin, M., Walzer, T. and Ugolini, S. (2008) Functions of Natural Killer Cells. Nature Immunology, 9, 503-510. [Google Scholar] [CrossRef] [PubMed]
[31] Crane, C.A., Han, S.J., Barry, J.J., Ahn, B.J. and Lanier L.L. (2010) TGF-Beta Downregulates the Activating Receptor NKG2D on NK Cells and CD8+ T Cells in Glioma Patients. Neuro-Oncology, 12, 7-13. [Google Scholar] [CrossRef] [PubMed]
[32] Gong, D., Shi, W., Yi, S.J., Chen, H., Groffen, J. and Heisterkamp, N. (2012) TGFbeta Signaling Plays a Critical Role in Promoting Alternative Macrophage Activation. BMC Immunology, 13, Article No. 31. [Google Scholar] [CrossRef] [PubMed]
[33] Lippitz, B.E. and Harris, R.A. (2016) Cytokine Patterns in Cancer Patients: A Review of the Correlation between Interleukin 6 and Prognosis. OncoImmunology, 5, e1093722. [Google Scholar] [CrossRef
[34] Kumari, N., Dwarakanath, B.S., Das, A. and Bhatt, A.N. (2016) Role of Interleukin-6 in Cancer Progression and Therapeutic Resistance. Tumor Biology, 37, 11553-11572. [Google Scholar] [CrossRef] [PubMed]
[35] Sakamoto, S., Kagawa, S., Kuwada, K., Ito, A., Kajioka, H., Kakiuchi, Y., Watanabe, M., Kagawa, T., Yoshida, R., Kikuchi, S., Kuroda, S., Tazawa, H. and Fujiwara, T. (2019) Intra-peritoneal Cancer-Immune Microenvironment Promotes Peritoneal Dissemination of Gastric Cancer. OncoImmunology, 8, e1671760. [Google Scholar] [CrossRef
[36] Na, Y.R., Lee, J.S., Lee, S.J., et al. (2013) Interleukin-6-Induced Twist and N-Cadherin Enhance Melanoma Cell Metastasis. Melanoma Research, 23, 434-443. [Google Scholar] [CrossRef
[37] Bromberg, J. and Wang, T.C. (2009) Inflammation and Cancer: IL-6 and STAT3 Complete the Link. Cancer Cell, 15, 79-80. [Google Scholar] [CrossRef] [PubMed]
[38] Huang, C., Yang, G., Jiang, T., Zhu, G., Li, H. and Qiu, Z. (2011) The Effects and Mechanisms of Blockage of STAT3 Signaling Pathway on IL-6 Inducing EMT in Human Pancreatic Cancer Cells in Vitro. Neoplasma, 58, 396-405. [Google Scholar] [CrossRef] [PubMed]
[39] Chang, Q., Daly, L. and Bromberg, J. (2014) The IL-6 Feed-Forward Loop: A Driver of Tumorigenesis. Seminars in Immunology, 26, 48-53. [Google Scholar] [CrossRef] [PubMed]
[40] Patel, S.A. and Gooderham, N.J. (2015) IL6 Mediates Immune and Colorectal Cancer Cell Cross-Talk via miR-21 and miR-29b. Molecular Cancer Research, 13, 1502-1508. [Google Scholar] [CrossRef
[41] Karakasheva, T.A., Lin, E.W., Tang, Q., Qiao, E., Waldron, T.J., Soni, M., Klein-Szanto, A.J., Sahu, V., Basu, D., Ohashi, S., Baba, K., Giaccone, Z.T., Walker, S.R., Frank, D.A., Wileyto, E.P., Long, Q., Dunagin, M.C., Raj, A., Diehl, J.A., Wong, K.K., Bass, A.J. and Rustgi, A.K. (2018) IL-6 Mediates Cross-Talk between Tumor Cells and Activated Fibroblasts in the Tumor Microenvironment. Cancer Research, 78, 4957-4970. [Google Scholar] [CrossRef
[42] Eskiler, G.G., Bezdegumeli, E., Ozman, Z., Ozkan, A.D., Bilir, C., Kucukakca, B.N., Ince, M.N., Men, A.Y., Aktas, O., Horoz, Y.E., Akpinar, D., Genc, I. and Kaleli, S. (2019) IL-6 Mediated JAK/STAT3 Signaling Pathway in Cancer Patients with Cachexia. Bratislava Medical Journal, 120, 819-826. [Google Scholar] [CrossRef
[43] De Vita, F., Romano, C., Orditura, M., Galizia, G., Martinelli, E., Lieto, E. and Catalano, G. (2001) Interleukin-6 Serum Level Correlates with Survival in Advanced Gastrointes-tinal Cancer Patients but Is Not an Independent Prognostic Indicator. Journal of Interferon & Cytokine Research, 21, 45-52. [Google Scholar] [CrossRef] [PubMed]
[44] Kitamura, H., Ohno, Y., Toyoshima, Y., Ohtake, J., Homma, S., Kawamura, H., Takahashi, N. and Taketomi, A. (2017) Interleukin-6/STAT3 Signaling as a Promising Target to Improve the Efficacy of Cancer Immunotherapy. Cancer Science, 108, 1947-1952. [Google Scholar] [CrossRef] [PubMed]
[45] Shang A, Wang W, Gu C, Chen C, Zeng B, Yang Y, et al. (2019) Long Non-Coding RNA HOTTIP Enhances IL-6 Expression to Potentiate Immune Escape of Ovarian Cancer Cells by Upreg-ulating the Expression of PD-L1 in Neutrophils. Journal of Experimental & Clinical Cancer Research, 38, Article No. 411. [Google Scholar] [CrossRef] [PubMed]
[46] Bharti, R., Dey, G. and Mandal, M. (2016) Cancer Development, Chemoresistance, Epithelial to Mesenchymal Transition and Stem Cells: A Snapshot of IL-6 Mediated Involvement. Cancer Letters, 375, 51-61. [Google Scholar] [CrossRef] [PubMed]
[47] Sun, J. and Fu, L. (2017) [IL-6 Promotes Gastric Cancer Cell Proliferation and EMT through Regulating miR-152/PIK3R3 Pathway]. Journal of Central South University (Medical Sciences), 42, 1241-1247.
[48] Kalluri, R. (2016) The Biology and Function of Fibroblasts in Cancer. Nature Reviews Cancer, 16, 582-598. [Google Scholar] [CrossRef] [PubMed]
[49] Wu, X., Tao, P., Zhou, Q., et al. (2017) IL-6 Secreted by Cancer-Associated Fibroblasts Promotes Epithelial-Mesenchymal Transition and Metastasis of Gastric Cancer via JAK2/STAT3 Signaling Pathway. Oncotarget, 8, 20741-20750. [Google Scholar] [CrossRef] [PubMed]