請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81785完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張永祺(Yung-Chi Chang) | |
| dc.contributor.author | Jui-I Lai | en |
| dc.contributor.author | 賴睿誼 | zh_TW |
| dc.date.accessioned | 2022-11-25T03:03:34Z | - |
| dc.date.available | 2026-08-24 | |
| dc.date.copyright | 2021-09-16 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-22 | |
| dc.identifier.citation | 1. Crocker, P.R., J.C. Paulson, and A. Varki, Siglecs and their roles in the immune system. Nat Rev Immunol, 2007. 7(4): p. 255-66. 2. Kelm, S., R. Schauer, J.C. Manuguerra, H.J. Gross, and P.R. Crocker, Modifications of cell surface sialic acids modulate cell adhesion mediated by sialoadhesin and CD22. Glycoconj J, 1994. 11(6): p. 576-85. 3. Macauley, M.S., P.R. Crocker, and J.C. Paulson, Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol, 2014. 14(10): p. 653-66. 4. Chang, Y.C., J. Olson, F.C. Beasley, C. Tung, J. Zhang, P.R. Crocker, A. Varki, and V. Nizet, Group B Streptococcus engages an inhibitory Siglec through sialic acid mimicry to blunt innate immune and inflammatory responses in vivo. PLoS Pathog, 2014. 10(1): p. e1003846. 5. Ali, S.R., J.J. Fong, A.F. Carlin, T.D. Busch, R. Linden, T. Angata, T. Areschoug, M. Parast, N. Varki, J. Murray, V. Nizet, and A. Varki, Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus. J Exp Med, 2014. 211(6): p. 1231-42. 6. Chen, G.Y., N.K. Brown, W. Wu, Z. Khedri, H. Yu, X. Chen, D. van de Vlekkert, A. D'Azzo, P. Zheng, and Y. Liu, Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1. Elife, 2014. 3: p. e04066. 7. Ishida, A., K. Akita, Y. Mori, S. Tanida, M. Toda, M. Inoue, and H. Nakada, Negative regulation of Toll-like receptor-4 signaling through the binding of glycosylphosphatidylinositol-anchored glycoprotein, CD14, with the sialic acid-binding lectin, CD33. J Biol Chem, 2014. 289(36): p. 25341-50. 8. Chen, G.Y., J. Tang, P. Zheng, and Y. Liu, CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science, 2009. 323(5922): p. 1722-5. 9. Fong, J.J., K. Sreedhara, L. Deng, N.M. Varki, T. Angata, Q. Liu, V. Nizet, and A. Varki, Immunomodulatory activity of extracellular Hsp70 mediated via paired receptors Siglec-5 and Siglec-14. EMBO J, 2015. 34(22): p. 2775-88. 10. Hinshaw, D.C. and L.A. Shevde, The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res, 2019. 79(18): p. 4557-4566. 11. Mantovani, A., F. Marchesi, A. Malesci, L. Laghi, and P. Allavena, Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol, 2017. 14(7): p. 399-416. 12. Bull, C., M.A. Stoel, M.H. den Brok, and G.J. Adema, Sialic acids sweeten a tumor's life. Cancer Res, 2014. 74(12): p. 3199-204. 13. Hakomori, S., Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. Cancer Res, 1996. 56(23): p. 5309-18. 14. Xiao, H., E.C. Woods, P. Vukojicic, and C.R. Bertozzi, Precision glycocalyx editing as a strategy for cancer immunotherapy. Proc Natl Acad Sci U S A, 2016. 113(37): p. 10304-9. 15. Jandus, C., K.F. Boligan, O. Chijioke, H. Liu, M. Dahlhaus, T. Demoulins, C. Schneider, M. Wehrli, R.E. Hunger, G.M. Baerlocher, H.U. Simon, P. Romero, C. Munz, and S. von Gunten, Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance. J Clin Invest, 2014. 124(4): p. 1810-20. 16. Laubli, H., O.M. Pearce, F. Schwarz, S.S. Siddiqui, L. Deng, M.A. Stanczak, L. Deng, A. Verhagen, P. Secrest, C. Lusk, A.G. Schwartz, N.M. Varki, J.D. Bui, and A. Varki, Engagement of myelomonocytic Siglecs by tumor-associated ligands modulates the innate immune response to cancer. Proc Natl Acad Sci U S A, 2014. 111(39): p. 14211-6. 17. Rodriguez, E., K. Boelaars, K. Brown, R.J. Eveline Li, L. Kruijssen, S.C.M. Bruijns, T. van Ee, S.T.T. Schetters, M.H.W. Crommentuijn, J.C. van der Horst, N.C.T. van Grieken, S.J. van Vliet, G. Kazemier, E. Giovannetti, J.J. Garcia-Vallejo, and Y. van Kooyk, Sialic acids in pancreatic cancer cells drive tumour-associated macrophage differentiation via the Siglec receptors Siglec-7 and Siglec-9. Nat Commun, 2021. 12(1): p. 1270. 18. Beatson, R., V. Tajadura-Ortega, D. Achkova, G. Picco, T.D. Tsourouktsoglou, S. Klausing, M. Hillier, J. Maher, T. Noll, P.R. Crocker, J. Taylor-Papadimitriou, and J.M. Burchell, The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9. Nat Immunol, 2016. 17(11): p. 1273-1281. 19. Takamiya, R., K. Ohtsubo, S. Takamatsu, N. Taniguchi, and T. Angata, The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-beta secretion from monocytes/macrophages through the DAP12-Syk pathway. Glycobiology, 2013. 23(2): p. 178-87. 20. Wang, J., J. Sun, L.N. Liu, D.B. Flies, X. Nie, M. Toki, J. Zhang, C. Song, M. Zarr, X. Zhou, X. Han, K.A. Archer, T. O'Neill, R.S. Herbst, A.N. Boto, M.F. Sanmamed, S. Langermann, D.L. Rimm, and L. Chen, Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nat Med, 2019. 25(4): p. 656-666. 21. Murray, P.J., J.E. Allen, S.K. Biswas, E.A. Fisher, D.W. Gilroy, S. Goerdt, S. Gordon, J.A. Hamilton, L.B. Ivashkiv, T. Lawrence, M. Locati, A. Mantovani, F.O. Martinez, J.L. Mege, D.M. Mosser, G. Natoli, J.P. Saeij, J.L. Schultze, K.A. Shirey, A. Sica, J. Suttles, I. Udalova, J.A. van Ginderachter, S.N. Vogel, and T.A. Wynn, Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity, 2014. 41(1): p. 14-20. 22. Martinez, F.O. and S. Gordon, The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep, 2014. 6: p. 13. 23. Xue, Q., Y. Yan, R. Zhang, and H. Xiong, Regulation of iNOS on Immune Cells and Its Role in Diseases. Int J Mol Sci, 2018. 19(12). 24. Cai, J., L. Xia, J. Li, S. Ni, H. Song, and X. Wu, Tumor-Associated Macrophages Derived TGF-betaInduced Epithelial to Mesenchymal Transition in Colorectal Cancer Cells through Smad2,3-4/Snail Signaling Pathway. Cancer Res Treat, 2019. 51(1): p. 252-266. 25. Chen, L., Y. Shi, X. Zhu, W. Guo, M. Zhang, Y. Che, L. Tang, X. Yang, Q. You, and Z. Liu, IL10 secreted by cancerassociated macrophages regulates proliferation and invasion in gastric cancer cells via cMet/STAT3 signaling. Oncol Rep, 2019. 42(2): p. 595-604. 26. Rapp, M., M.W.M. Wintergerst, W.G. Kunz, V.K. Vetter, M.M.L. Knott, D. Lisowski, S. Haubner, S. Moder, R. Thaler, S. Eiber, B. Meyer, N. Rohrle, I. Piseddu, S. Grassmann, P. Layritz, B. Kuhnemuth, S. Stutte, C. Bourquin, U.H. von Andrian, S. Endres, and D. Anz, CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes. J Exp Med, 2019. 216(5): p. 1170-1181. 27. Warnecke, A., S. Abele, S. Musunuri, J. Bergquist, and R.A. Harris, Scavenger Receptor A Mediates the Clearance and Immunological Screening of MDA-Modified Antigen by M2-Type Macrophages. Neuromolecular Med, 2017. 19(4): p. 463-479. 28. Roszer, T., Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms. Mediators Inflamm, 2015. 2015: p. 816460. 29. Jager, N.A., B.M. Wallis de Vries, J.L. Hillebrands, N.J. Harlaar, R.A. Tio, R.H. Slart, G.M. van Dam, H.H. Boersma, C.J. Zeebregts, and J. Westra, Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets. Mol Imaging Biol, 2016. 18(2): p. 283-91. 30. Kvorjak, M., Y. Ahmed, M.L. Miller, R. Sriram, C. Coronnello, J.G. Hashash, D.J. Hartman, C.A. Telmer, N. Miskov-Zivanov, O.J. Finn, and S. Cascio, Cross-talk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer. Cancer Immunol Res, 2020. 8(2): p. 167-178. 31. Movahedi, K., D. Laoui, C. Gysemans, M. Baeten, G. Stange, J. Van den Bossche, M. Mack, D. Pipeleers, P. In't Veld, P. De Baetselier, and J.A. Van Ginderachter, Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res, 2010. 70(14): p. 5728-39. 32. Noy, R. and J.W. Pollard, Tumor-associated macrophages: from mechanisms to therapy. Immunity, 2014. 41(1): p. 49-61. 33. Wang, X.F., H.S. Wang, H. Wang, F. Zhang, K.F. Wang, Q. Guo, G. Zhang, S.H. Cai, and J. Du, The role of indoleamine 2,3-dioxygenase (IDO) in immune tolerance: focus on macrophage polarization of THP-1 cells. Cell Immunol, 2014. 289(1-2): p. 42-8. 34. Angata, T., T. Hayakawa, M. Yamanaka, A. Varki, and M. Nakamura, Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates. FASEB J, 2006. 20(12): p. 1964-73. 35. Yamanaka, M., Y. Kato, T. Angata, and H. Narimatsu, Deletion polymorphism of SIGLEC14 and its functional implications. Glycobiology, 2009. 19(8): p. 841-6. 36. Angata, T., T. Ishii, T. Motegi, R. Oka, R.E. Taylor, P.C. Soto, Y.C. Chang, I. Secundino, C.X. Gao, K. Ohtsubo, S. Kitazume, V. Nizet, A. Varki, A. Gemma, K. Kida, and N. Taniguchi, Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation. Cell Mol Life Sci, 2013. 70(17): p. 3199-210. 37. Rodrigues, E. and M.S. Macauley, Hypersialylation in Cancer: Modulation of Inflammation and Therapeutic Opportunities. Cancers (Basel), 2018. 10(6). 38. Chen, Y., Y. Song, W. Du, L. Gong, H. Chang, and Z. Zou, Tumor-associated macrophages: an accomplice in solid tumor progression. J Biomed Sci, 2019. 26(1): p. 78. 39. Subramanian, A., P. Tamayo, V.K. Mootha, S. Mukherjee, B.L. Ebert, M.A. Gillette, A. Paulovich, S.L. Pomeroy, T.R. Golub, E.S. Lander, and J.P. Mesirov, Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A, 2005. 102(43): p. 15545-50. 40. Rogerieux, F., M. Belaise, H. Terzidis-Trabelsi, A. Greffard, Y. Pilatte, and C.R. Lambre, Determination of the sialic acid linkage specificity of sialidases using lectins in a solid phase assay. Anal Biochem, 1993. 211(2): p. 200-4. 41. Lian, G., S. Chen, M. Ouyang, F. Li, L. Chen, and J. Yang, Colon Cancer Cell Secretes EGF to Promote M2 Polarization of TAM Through EGFR/PI3K/AKT/mTOR Pathway. Technol Cancer Res Treat, 2019. 18: p. 1533033819849068. 42. Zhang, Y., S. Choksi, K. Chen, Y. Pobezinskaya, I. Linnoila, and Z.G. Liu, ROS play a critical role in the differentiation of alternatively activated macrophages and the occurrence of tumor-associated macrophages. Cell Res, 2013. 23(7): p. 898-914. 43. Fraschilla, I. and S. Pillai, Viewing Siglecs through the lens of tumor immunology. Immunol Rev, 2017. 276(1): p. 178-191. 44. Pearce, O.M. and H. Laubli, Sialic acids in cancer biology and immunity. Glycobiology, 2016. 26(2): p. 111-28. 45. Piccolo, E., N. Tinari, D. Semeraro, S. Traini, I. Fichera, A. Cumashi, R. La Sorda, F. Spinella, A. Bagnato, R. Lattanzio, M. D'Egidio, A. Di Risio, P. Stampolidis, M. Piantelli, C. Natoli, A. Ullrich, and S. Iacobelli, LGALS3BP, lectin galactoside-binding soluble 3 binding protein, induces vascular endothelial growth factor in human breast cancer cells and promotes angiogenesis. J Mol Med (Berl), 2013. 91(1): p. 83-94. 46. Traini, S., E. Piccolo, N. Tinari, C. Rossi, R. La Sorda, F. Spinella, A. Bagnato, R. Lattanzio, M. D'Egidio, A. Di Risio, F. Tomao, A. Grassadonia, M. Piantelli, C. Natoli, and S. Iacobelli, Inhibition of tumor growth and angiogenesis by SP-2, an anti-lectin, galactoside-binding soluble 3 binding protein (LGALS3BP) antibody. Mol Cancer Ther, 2014. 13(4): p. 916-25. 47. Laubli, H., F. Alisson-Silva, M.A. Stanczak, S.S. Siddiqui, L. Deng, A. Verhagen, N. Varki, and A. Varki, Lectin galactoside-binding soluble 3 binding protein (LGALS3BP) is a tumor-associated immunomodulatory ligand for CD33-related Siglecs. J Biol Chem, 2014. 289(48): p. 33481-91. 48. Loimaranta, V., J. Hepojoki, O. Laaksoaho, and A.T. Pulliainen, Galectin-3-binding protein: A multitask glycoprotein with innate immunity functions in viral and bacterial infections. J Leukoc Biol, 2018. 104(4): p. 777-786. 49. Bull, C., T.J. Boltje, N. Balneger, S.M. Weischer, M. Wassink, J.J. van Gemst, V.R. Bloemendal, L. Boon, J. van der Vlag, T. Heise, M.H. den Brok, and G.J. Adema, Sialic Acid Blockade Suppresses Tumor Growth by Enhancing T-cell-Mediated Tumor Immunity. Cancer Res, 2018. 78(13): p. 3574-3588. 50. Martin, L.T., J.D. Marth, A. Varki, and N.M. Varki, Genetically altered mice with different sialyltransferase deficiencies show tissue-specific alterations in sialylation and sialic acid 9-O-acetylation. J Biol Chem, 2002. 277(36): p. 32930-8. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81785 | - |
| dc.description.abstract | Siglec是表現於免疫細胞表面的唾液酸化受體，能藉由下游的訊息傳遞來影響免疫細胞的功能，其中Siglec-5和Siglec-14為巨噬細胞表面的配對型受體，由於兩者位於N端的配體結合位序列相似，因此能結合幾乎相同的配體，並經由膜內傳遞抑制訊息的ITIM motif和傳遞活化訊息的ITAM motif來調控巨噬細胞的表型。目前已知腫瘤細胞表面會大量表現唾液酸化修飾物質，並且與腫瘤微環境中巨噬細胞表面的Siglec產生交互作用，使其極化成腫瘤相關巨噬細胞來抑制抗腫瘤的反應，因此本篇論文想要探討傳遞相反訊息的Siglec-5/14配對型受體會如何影響腫瘤微環境中巨噬細胞的極化。我們利用大腸直腸癌細胞株SW620的培養液來刺激THP-1細胞，藉此模擬腫瘤微環境所造成的影響，首先偵測了腫瘤相關巨噬細胞相關的細胞激素及因子的表現，我們發現表現Siglec-14的THP-1細胞相較於表現Siglec-5的THP-1細胞能分泌較多腫瘤相關巨噬細胞指標，如CCL22、IL-10、VEGFA等，並且Siglec-14在腫瘤細胞培養液的刺激下會藉由SYK激酶來活化下游的訊息路徑。另一方面，我們發現腫瘤細胞培養液中含有大量的唾液酸化修飾物質，其中Gal-3BP為Siglec-5和Siglec-14的配體。因此目前我們已經發現，腫瘤細胞所分泌的物質能透過結合巨噬細胞表面的Siglec-14來造成腫瘤巨噬細胞的極化，然而目前尚未能確定Gal-3BP與Siglec-14的交互作用是否是造成巨噬細胞極化的主要原因，有待後續實驗釐清。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T03:03:34Z (GMT). No. of bitstreams: 1 U0001-1908202115493600.pdf: 4577452 bytes, checksum: bf23c7db593892330259b653abd01de9 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 口試委員審定書 i 致謝 ii 中文摘要 iii Abstract iv 目錄 v 壹、研究背景及動機 1 一、 Sialic acid-binding immunoglobulin-like lectin (Siglec)受體 1 1. Siglec簡介 1 2. Siglec與先天性免疫抗菌反應之關係 2 3. Siglec與自體相關分子模式 (self-associated molecular patterns，SAMPs)和損害相關分子模式 (damage-associated molecular patterns，DAMPs)之關係 2 4. Siglec與腫瘤免疫之關係 3 二、巨噬細胞 5 1. 巨噬細胞極化 (Macrophage polarization) 5 2. 腫瘤相關巨噬細胞 6 三、 研究動機 7 1. Siglec-5和Siglec-14配對型受體 (paired receptor) 7 2. 研究假說 8 貳、實驗材料及研究方法 9 一、 實驗材料 9 1. 細胞株 (Cell lines) 9 2. 抗體 (Antibodies) 9 3. 酵素免疫分析法套組 (ELISA kits) 10 4. 引子 (Primers) 10 5. 基因敲落載體 (shRNA vector clone) 11 6. 質體 (Plasmid) 11 二、 實驗方法 12 1. 利用腫瘤細胞培養液處理巨噬細胞 12 2. 細胞生長曲線 12 3. 流式細胞分析 (FACS) 12 4. RNA萃取與即時定量聚合酶連鎖反應 (RT-qPCR) 13 5. 西方墨點法 (Western blot) 13 6. 酵素免疫分析法 (ELISA) 14 7. Bulk RNA sequencing與結果分析 14 8. 免疫沉澱法 (Immunoprecipitation，IP) 16 9. 銀染 (Silver stain) 17 10. 質譜分析 (Mass spectrometry) 17 11. Siglec-14 Fc融合蛋白純化 17 12. Gal-3BP基因敲落 (Gal-3BP gene knockdown) 18 13. Gal-3BP基因敲除 (Gal-3BP gene knockout) 19 參、 研究結果 21 一、Siglec-5與Siglec-14對巨噬細胞極化的影響 21 1. Siglec-14促使THP-1在SW620 CM處理下表現較多與腫瘤相關巨噬細胞(TAM)功能相關的激素及指標 21 2. RNA定序偵測EV/THP-1、S5/THP-1、S14/THP-1在SW620 CM處理下之基因表現 22 3. Siglec-14促使THP-1在SW620 CM處理下提升SYK磷酸化程度 24 二、 SW620 CM中Siglec-5/14配體之偵測 25 三、Gal-3BP與Siglec-14對巨噬細胞極化的影響 26 1. SW620/Gal-3BPKD CM處理下仍可促使S14/THP-1細胞產生高量的CCL22 26 2. SW620/Gal-3BPKO CM處理下仍可促使S14/THP-1細胞產生高量的CCL22 27 3. Siglec-5/14中和抗體可以抑制S14/THP-1因SW620 CM處理後所產生的TAM功能相關的指標 27 肆、討論與未來方向 28 參考文獻 32 結果圖表 37 附錄 59 | |
| dc.language.iso | zh-TW | |
| dc.subject | 腫瘤相關巨噬細胞 | zh_TW |
| dc.subject | Siglec-14 | zh_TW |
| dc.subject | Siglec-5 | zh_TW |
| dc.subject | Gal-3BP | zh_TW |
| dc.subject | 巨噬細胞極化 | zh_TW |
| dc.subject | Siglec-5 | en |
| dc.subject | tumor-associated macrophage | en |
| dc.subject | macrophage polarization | en |
| dc.subject | Siglec-14 | en |
| dc.subject | Gal-3BP | en |
| dc.title | Siglec-14在大腸直腸癌細胞培養液刺激下促進腫瘤相關巨噬細胞極化 | zh_TW |
| dc.title | Siglec-14 promotes tumor-associated macrophage polarization upon stimulation with colorectal cancer conditioned medium | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林琬琬(Hsin-Tsai Liu),陳念榮(Chih-Yang Tseng) | |
| dc.subject.keyword | Siglec-5,Siglec-14,巨噬細胞極化,腫瘤相關巨噬細胞,Gal-3BP, | zh_TW |
| dc.subject.keyword | Siglec-5,Siglec-14,macrophage polarization,tumor-associated macrophage,Gal-3BP, | en |
| dc.relation.page | 61 | |
| dc.identifier.doi | 10.6342/NTU202102517 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-08-23 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| dc.date.embargo-lift | 2026-08-24 | - |
| 顯示於系所單位： | 微生物學科所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-1908202115493600.pdf 此日期後於網路公開 2026-08-24 | 4.47 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。