肿瘤相关性中性粒细胞促肿瘤转移机制的研究进展
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摘要
中性粒细胞是循环中最为丰富的白细胞,在机体的免疫反应中发挥重要作用。中性粒细胞不仅参与免疫反应,也在肿瘤的发生发展,特别是侵袭和转移过程中发挥重要作用。中性粒细胞可分化为N1和N2亚型,在肿瘤的转移中表现出抑制转移(N1)和促进转移(N2)两种截然不同的的作用。但肿瘤相关中性粒细胞(tumor-associated neutrophils,TANs)在肿瘤转移机制中发挥的作用相对比较复杂,尚缺乏系统阐述。本文主要介绍TANs,分析其在肿瘤转移过程中促进肿瘤发生侵袭和转移的机制,对TANs作为抗肿瘤治疗策略的可能性进行综述。
Neutrophils are the most abundant leukocytes in the peripheral blood and play an important role in the immune response.However, there is growing evidence indicating that in addition to the immune response, neutrophils also have a crucial role in tumor development, especially in the process of invasion and metastasis. According to current research, depending on their phenotype, neutrophils appear to be either anti-metastasis(N1) or pro-metastasis(N2). However, the role of tumor-associated neutrophils(TANs) in the metastasis of tumors is relatively complex and lacks a systematic introduction. This review mainly introduces TANs and focuses on the mechanism of TANs in promoting tumor invasion and metastasis. Finally, the possibility of TANs as an anti-tumor treatment strategy is discussed.
Neutrophils are the most abundant leukocytes in the peripheral blood and play an important role in the immune response.However, there is growing evidence indicating that in addition to the immune response, neutrophils also have a crucial role in tumor development, especially in the process of invasion and metastasis. According to current research, depending on their phenotype, neutrophils appear to be either anti-metastasis(N1) or pro-metastasis(N2). However, the role of tumor-associated neutrophils(TANs) in the metastasis of tumors is relatively complex and lacks a systematic introduction. This review mainly introduces TANs and focuses on the mechanism of TANs in promoting tumor invasion and metastasis. Finally, the possibility of TANs as an anti-tumor treatment strategy is discussed.
引文
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[19] Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche[J]. Cancer Cell, 2016, 30(5):668-681.
[20] Zhang W, Gu J, Chen J, et al. Interaction with neutrophils promotes gastric cancer cell migration and invasion by inducing epithelialmesenchymal transition[J]. Oncol Rep, 2017, 38(5):2959-2966.
[21] Wada Y, Yoshida K, Tsutani Y, et al. Neutrophil elastase induces cell proliferation and migration by the release of TGF-alpha, PDGF and VEGF in esophageal cell lines[J]. Oncol Rep, 2007, 17(1):161-167.
[22] Uribe-Querol E, Rosales C. Neutrophils in cancer:two sides of the same coin[J]. J Immunol Res, 2015, 2015:983698.
[23] Zhang J, Qiao X, Shi H, et al. Circulating tumor-associated neutrophils(cTAN)contribute to circulating tumor cell survival by suppressing peripheral leukocyte activation[J]. Tumour Biol, 2016, 37(4):5397-5404.
[24] Jablonska J, Lang S, Sionov RV, et al. The regulation of pre-metastatic niche formation by neutrophils[J]. Oncotarget, 2017, 8(67):112132-112144.
[25] Peinado H, Zhang H, Matei IR, et al. Pre-metastatic niches:organspecific homes for metastases[J]. Nat Rev Cancer, 2017, 17(5):302-317.
[26] Wu CF, Andzinski L, Kasnitz N, et al. The lack of typeⅠinterferon induces neutrophil-mediated pre-metastatic niche formation in the mouse lung[J]. Int J Cancer, 2015, 137(4):837-847.
[27] Singel KL, Segal BH. Neutrophils in the tumor microenvironment:trying to heal the wound that cannot heal[J]. Immunol Rev, 2016, 273(1):329-343.
[28] Wang TT, Zhao YL, Peng LS, et al. Tumour-activated neutrophils in gastric cancer foster immune suppression and disease progression through GM-CSF-PD-L1 pathway[J]. Gut, 2017, 66(11):1900-1911.
[29] Kuang DM, Zhao Q, Wu Y, et al. Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma[J]. J Hepatol, 2011, 54(5):948-955.
[30] Seignez C, Phillipson M. The multitasking neutrophils and their involvement in angiogenesis[J]. Curr Opin Hematol, 2017, 24(1):3-8.
[31] Hegde PS, Wallin JJ, Mancao C. Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics[J].Semin Cancer Biol, 2018, 52(Pt 2):117-124.
[32] Queen MM, Ryan RE, Holzer RG, et al. Breast cancer cells stimulate neutrophils to produce oncostatin M:potential implications for tumor progression[J]. Cancer Res, 2005, 65(19):8896-8904.
[33] Shojaei F, Wu X, Zhong C, et al. Bv8 regulates myeloid-cell-dependent tumour angiogenesis[J]. Nature, 2007, 450(7171):825-831.
[34] Fridlender ZG, Albelda SM. Tumor-associated neutrophils:friend or foe[J]? Carcinogenesis, 2012, 33(5):949-955.
[35] Brandsma AM, Ten Broeke T, Nederend M, et al. Simultaneous targeting of fcgammars and fcalphari enhances tumor cell killing[J]. Cancer Immunol Res, 2015, 3(12):1316-1322.
[2] Tecchio C, Scapini P, Pizzolo G, et al. On the cytokines produced by human neutrophils in tumors[J]. Semin Cancer Biol, 2013, 23(3):159-170.
[3] Sagiv JY, Michaeli J, Assi S, et al. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer[J]. Cell Rep, 2015, 10(4):562-573.
[4] Moses K, Brandau S. Human neutrophils:their role in cancer and relation to myeloid-derived suppressor cells[J]. Semin Immunol, 2016,28(2):187-196.
[5] Fridlender ZG, Sun J, Mishalian I, et al. Transcriptomic analysis comparing tumor-associated neutrophils with granulocytic myeloid-derived suppressor cells and normal neutrophils[J]. PLo S One, 2012, 7(2):e31524.
[6] Hagerling C, Werb Z. Neutrophils:critical components in experimental animal models of cancer[J]. Semin Immunol, 2016, 28(2):197-204.
[7] Jackaman C, Tomay F, Duong L, et al. Aging and cancer:the role of macrophages and neutrophils[J]. Ageing Res Rev, 2017,(36):105-116.
[8] Granot Z, Fridlender ZG. Plasticity beyond cancer cells and the"immunosuppressive switch"[J]. Cancer Res, 2015, 75(21):4441-4445.
[9] ME S, L L, J S, et al. Tumor-associated neutrophils display a distinct N1profile following TGFβmodulation:a transcriptomics analysis of provs. antitumor TANs[J]. Oncoimmunology, 2016, 5(11):e1232221.
[10] DR P, A H. Neutrophils in the tumor microenvironment[J]. Trends Immunol, 2016, 37(1):41-52.
[11] Liang W, Ferrara N. The complex role of neutrophils in tumor angiogenesis and metastasis[J]. Cancer Immunol Res, 2016, 4(2):83-91.
[12] Ekaterina P, Stephan L, Jadwiga J. The essential role of typeⅠinterferons in differentiation and activation of tumor-associated neutrophils[J]. Front Immunol, 2016,(7):629.
[13] Shen M, Hu P, Donskov F, et al. Tumor-associated neutrophils as a new prognostic factor in cancer:a systematic review and meta-analysis[J].PLoS One, 2014, 9(6):e98259.
[14] Abe H, Morikawa T, Saito R, et al. In Epstein-Barr virus-associated gastric carcinoma a high density of CD66b-positive tumor-associated neutrophils is associated with intestinal-type histology and low frequency of lymph node metastasis[J]. Virchows Arch, 2016, 468(5):539-548.
[15] Li S, Cong XL, Gao HY, et al. Tumor-associated neutrophils induce EMT by IL-17a to promote migration and invasion in gastric cancer cells[J].J Exp Clin Cancer Res, 2019, 38(1):6-10.
[16] Muhammad N, Farah F. Extracellular vesicles, tunneling nanotubes, and cellular interplay:synergies and missing links[J]. Front Mole Biosci,2017,(4):50-56.
[17] Laura N, Alberto BM, Marta HM, et al. The influence of tumour-derived extracellular vesicles on local and distal metastatic dissemination[J].Mol Aspects Med, 2018, 60:15-26.
[18] Sakai C, Nishikawa H. Immunosuppressive environment in tumors[J].Gan to kagaku ryoho. Cancer&chemotherapy, 2018, 45(2):222-226.
[19] Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche[J]. Cancer Cell, 2016, 30(5):668-681.
[20] Zhang W, Gu J, Chen J, et al. Interaction with neutrophils promotes gastric cancer cell migration and invasion by inducing epithelialmesenchymal transition[J]. Oncol Rep, 2017, 38(5):2959-2966.
[21] Wada Y, Yoshida K, Tsutani Y, et al. Neutrophil elastase induces cell proliferation and migration by the release of TGF-alpha, PDGF and VEGF in esophageal cell lines[J]. Oncol Rep, 2007, 17(1):161-167.
[22] Uribe-Querol E, Rosales C. Neutrophils in cancer:two sides of the same coin[J]. J Immunol Res, 2015, 2015:983698.
[23] Zhang J, Qiao X, Shi H, et al. Circulating tumor-associated neutrophils(cTAN)contribute to circulating tumor cell survival by suppressing peripheral leukocyte activation[J]. Tumour Biol, 2016, 37(4):5397-5404.
[24] Jablonska J, Lang S, Sionov RV, et al. The regulation of pre-metastatic niche formation by neutrophils[J]. Oncotarget, 2017, 8(67):112132-112144.
[25] Peinado H, Zhang H, Matei IR, et al. Pre-metastatic niches:organspecific homes for metastases[J]. Nat Rev Cancer, 2017, 17(5):302-317.
[26] Wu CF, Andzinski L, Kasnitz N, et al. The lack of typeⅠinterferon induces neutrophil-mediated pre-metastatic niche formation in the mouse lung[J]. Int J Cancer, 2015, 137(4):837-847.
[27] Singel KL, Segal BH. Neutrophils in the tumor microenvironment:trying to heal the wound that cannot heal[J]. Immunol Rev, 2016, 273(1):329-343.
[28] Wang TT, Zhao YL, Peng LS, et al. Tumour-activated neutrophils in gastric cancer foster immune suppression and disease progression through GM-CSF-PD-L1 pathway[J]. Gut, 2017, 66(11):1900-1911.
[29] Kuang DM, Zhao Q, Wu Y, et al. Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma[J]. J Hepatol, 2011, 54(5):948-955.
[30] Seignez C, Phillipson M. The multitasking neutrophils and their involvement in angiogenesis[J]. Curr Opin Hematol, 2017, 24(1):3-8.
[31] Hegde PS, Wallin JJ, Mancao C. Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics[J].Semin Cancer Biol, 2018, 52(Pt 2):117-124.
[32] Queen MM, Ryan RE, Holzer RG, et al. Breast cancer cells stimulate neutrophils to produce oncostatin M:potential implications for tumor progression[J]. Cancer Res, 2005, 65(19):8896-8904.
[33] Shojaei F, Wu X, Zhong C, et al. Bv8 regulates myeloid-cell-dependent tumour angiogenesis[J]. Nature, 2007, 450(7171):825-831.
[34] Fridlender ZG, Albelda SM. Tumor-associated neutrophils:friend or foe[J]? Carcinogenesis, 2012, 33(5):949-955.
[35] Brandsma AM, Ten Broeke T, Nederend M, et al. Simultaneous targeting of fcgammars and fcalphari enhances tumor cell killing[J]. Cancer Immunol Res, 2015, 3(12):1316-1322.
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