REFERENCES
1. DeOliveira ML, Cunningham SC, Cameron JL, et al. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 2007;245:755-62.
2. Khan SA, Tavolari S, Brandi G. Cholangiocarcinoma: epidemiology and risk factors. Liver Int 2019;39 Suppl 1:19-31.
4. Wang Y, Yang H, Shen C, Luo J. Surgical procedure and long-term survival of hilar cholangiocarcinoma. Int J Clin Exp Med 2015;8:1122-8.
5. Homayounfar K, Gunawan B, Cameron S, et al. Pattern of chromosomal aberrations in primary liver cancers identified by comparative genomic hybridization. Hum Pathol 2009;40:834-42.
6. Uhm KO, Park YN, Lee JY, Yoon DS, Park SH. Chromosomal imbalances in Korean intrahepatic cholangiocarcinoma by comparative genomic hybridization. Cancer Genet Cytogenet 2005;157:37-41.
7. Vilà P, Ravichandra A, Agirre Lizaso A, Perugorria MJ, Affò S. Heterogeneity, crosstalk, and targeting of cancer-associated fibroblasts in cholangiocarcinoma. Hepatology 2023;Online ahead of print.
8. Nakazawa K, Dobashi Y, Suzuki S, Fujii H, Takeda Y, Ooi A. Amplification and overexpression of c-erbB-2, epidermal growth factor receptor, and c-met in biliary tract cancers. J Pathol 2005;206:356-65.
9. Brandi G, Farioli A, Astolfi A, Biasco G, Tavolari S. Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies. Oncotarget 2015;6:14744-53.
10. O'Rourke CJ, Munoz-Garrido P, Aguayo EL, Andersen JB. Epigenome dysregulation in cholangiocarcinoma. Biochim Biophys Acta Mol Basis Dis 2018;1864:1423-34.
11. Chen Z, Guo P, Xie X, Yu H, Wang Y, Chen G. The role of tumour microenvironment: a new vision for cholangiocarcinoma. J Cell Mol Med 2019;23:59-69.
12. Leyva-Illades D, McMillin M, Quinn M, Demorrow S. Cholangiocarcinoma pathogenesis: role of the tumor microenvironment. Transl Gastrointest Cancer 2012;1:71-80.
13. Kai F, Drain AP, Weaver VM. The extracellular matrix modulates the metastatic journey. Dev Cell 2019;49:332-46.
14. Wang J, Ilyas S. Targeting the tumor microenvironment in cholangiocarcinoma: implications for therapy. Expert Opin Investig Drugs 2021;30:429-38.
15. Naba A, Clauser KR, Ding H, Whittaker CA, Carr SA, Hynes RO. The extracellular matrix: tools and insights for the "omics" era. Matrix Biol 2016;49:10-24.
16. Mouw JK, Ou G, Weaver VM. Extracellular matrix assembly: a multiscale deconstruction. Nat Rev Mol Cell Biol 2014;15:771-85.
17. Hastings JF, Skhinas JN, Fey D, Croucher DR, Cox TR. The extracellular matrix as a key regulator of intracellular signalling networks. Br J Pharmacol 2019;176:82-92.
18. Cox TR, Erler JT. Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer. Dis Model Mech 2011;4:165-78.
21. Winkler J, Abisoye-Ogunniyan A, Metcalf KJ, Werb Z. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat Commun 2020;11:5120.
22. Awaji M, Saxena S, Wu L, et al. CXCR2 signaling promotes secretory cancer-associated fibroblasts in pancreatic ductal adenocarcinoma. FASEB J 2020;34:9405-18.
23. Colyn L, Alvarez-Sola G, Latasa MU, et al. New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming. J Exp Clin Cancer Res 2022;41:183.
24. Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010;141:52-67.
25. Sirica AE, Gores GJ. Desmoplastic stroma and cholangiocarcinoma: clinical implications and therapeutic targeting. Hepatology 2014;59:2397-402.
26. Subrungruanga I, Thawornkunob C, Chawalitchewinkoon-Petmitrc P, Pairojkul C, Wongkham S, Petmitrb S. Gene expression profiling of intrahepatic cholangiocarcinoma. Asian Pac J Cancer Prev 2013;14:557-63.
27. Islam K, Thummarati P, Kaewkong P, Sripa B, Suthiphongchai T. Role of laminin and cognate receptors in cholangiocarcinoma cell migration. Cell Adh Migr 2021;15:152-65.
28. Liu W, Tian F, Jiang P, et al. Aberrant expression of laminin γ2 correlates with poor prognosis and promotes invasion in extrahepatic cholangiocarcinoma. J Surg Res 2014;186:150-6.
29. Li Y, Li DJ, Chen J, et al. Expression of lamininγ2 in extrahepatic cholangiocarcinoma tissues and its influence on tumor invasion and metastasis. Asian Pac J Cancer Prev 2015;16:2099-102.
30. Aishima S, Matsuura S, Terashi T, et al. Aberrant expression of laminin gamma 2 chain and its prognostic significance in intrahepatic cholangiocarcinoma according to growth morphology. Mod Pathol 2004;17:938-45.
31. Pei YF, Liu J, Cheng J, Wu WD, Liu XQ. Silencing of LAMC2 reverses epithelial-mesenchymal transition and inhibits angiogenesis in cholangiocarcinoma via inactivation of the epidermal growth factor receptor signaling pathway. Am J Pathol 2019;189:1637-53.
32. Yoo HJ, Yun BR, Kwon JH, et al. Genetic and expression alterations in association with the sarcomatous change of cholangiocarcinoma cells. Exp Mol Med 2009;41:102-15.
33. Ding YB, Deng B, Huang YS, et al. A high level of integrin α6 expression in human intrahepatic cholangiocarcinoma cells is associated with a migratory and invasive phenotype. Dig Dis Sci 2013;58:1627-35.
34. Soejima Y, Inoue M, Takahashi Y, Uozaki H, Sawabe M, Fukusato T. Integrins αvβ6, α6β4 and α3β1 are down-regulated in cholangiolocellular carcinoma but not cholangiocarcinoma. Hepatol Res 2014;44:E320-34.
35. Li D, Chen J, Gao Z, et al. 67-kDa laminin receptor in human bile duct carcinoma. Eur Surg Res 2009;42:168-73.
36. Neve A, Cantatore FP, Maruotti N, Corrado A, Ribatti D. Extracellular matrix modulates angiogenesis in physiological and pathological conditions. Biomed Res Int 2014;2014:756078.
37. Lv H, Yu G, Sun L, Zhang Z, Zhao X, Chai W. Elevate level of glycosaminoglycans and altered sulfation pattern of chondroitin sulfate are associated with differentiation status and histological type of human primary hepatic carcinoma. Oncology 2007;72:347-56.
38. Nagarajan A, Malvi P, Wajapeyee N. Heparan sulfate and heparan sulfate proteoglycans in cancer initiation and progression. Front Endocrinol 2018;9:483.
39. Sabit H, Tsuneyama K, Shimonishi T, et al. Enhanced expression of basement-membrane-type heparan sulfate proteoglycan in tumor fibro-myxoid stroma of intrahepatic cholangiocarcinoma. Pathol Int 2001;51:248-56.
40. Batmunkh E, Tátrai P, Szabó E, et al. Comparison of the expression of agrin, a basement membrane heparan sulfate proteoglycan, in cholangiocarcinoma and hepatocellular carcinoma. Hum Pathol 2007;38:1508-15.
42. Huleihel L, Hussey GS, Naranjo JD, et al. Matrix-bound nanovesicles within ECM bioscaffolds. Sci Adv 2016;2:e1600502.
43. Martino MM, Hubbell JA. The 12th-14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain. FASEB J 2010;24:4711-21.
44. Mott JD, Werb Z. Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 2004;16:558-64.
46. Perez S. The clinician and caries. Self-test of his diagnostic method. Chir Dent Fr 1989;59:35-7.
47. Sun Q, Zhao C, Xia L, et al. High expression of matrix metalloproteinase-9 indicates poor prognosis in human hilar cholangiocarcinoma. Int J Clin Exp Pathol 2014;7:6157-64.
48. Kirimlioğlu H, Türkmen I, Başsüllü N, Dirican A, Karadağ N, Kirimlioğlu V. The expression of matrix metalloproteinases in intrahepatic cholangiocarcinoma, hilar (Klatskin tumor), middle and distal extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma: role of matrix metalloproteinases in tumor progression and prognosis. Turk J Gastroenterol 2009;20:41-7.
49. Prakobwong S, Yongvanit P, Hiraku Y, et al. Involvement of MMP-9 in peribiliary fibrosis and cholangiocarcinogenesis via Rac1-dependent DNA damage in a hamster model. Int J Cancer 2010;127:2576-87.
50. Pak JH, Shin J, Song IS, Shim S, Jang SW. Clonorchis sinensis excretory-secretory products regulate migration and invasion in cholangiocarcinoma cells via extracellular signal-regulated kinase 1/2/nuclear factor-κB-dependent matrix metalloproteinase-9 expression. Int J Parasitol 2017;47:51-9.
51. Lin HY, Li CJ, Yang YL, Huang YH, Hsiau YT, Chu PY. Roles of lysyl oxidase family members in the tumor microenvironment and progression of liver cancer. Int J Mol Sci 2020;21:9751.
52. Bergeat D, Fautrel A, Turlin B, et al. Impact of stroma LOXL2 overexpression on the prognosis of intrahepatic cholangiocarcinoma. J Surg Res 2016;203:441-50.
53. Xu J, Li D, Li X, et al. 67 laminin receptor promotes the malignant potential of tumour cells up-regulating lysyl oxidase-like 2 expression in cholangiocarcinoma. Dig Liver Dis 2014;46:750-7.
54. Peng T, Deng X, Tian F, et al. The interaction of LOXL2 with GATA6 induces VEGFA expression and angiogenesis in cholangiocarcinoma. Int J Oncol 2019;55:657-70.
55. Chakraborty S, Njah K, Hong W. Agrin mediates angiogenesis in the tumor microenvironment. Trends Cancer 2020;6:81-5.
56. Sirica AE. Matricellular proteins in intrahepatic cholangiocarcinoma. Hepatobiliary cancers: translational advances and molecular medicine. Elsevier; 2022. pp. 249-81.
57. Albrengues J, Shields MA, Ng D, et al. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science 2018;361:eaao4227.
58. Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 2002;3:349-63.
59. Strutz F, Okada H, Lo CW, et al. Identification and characterization of a fibroblast marker: FSP1. J Cell Biol 1995;130:393-405.
60. Nishihara Y, Aishima S, Hayashi A, et al. CD10+ fibroblasts are more involved in the progression of hilar/extrahepatic cholangiocarcinoma than of peripheral intrahepatic cholangiocarcinoma. Histopathology 2009;55:423-31.
61. Pietras K, Sjöblom T, Rubin K, Heldin CH, Ostman A. PDGF receptors as cancer drug targets. Cancer Cell 2003;3:439-43.
62. Augsten M. Cancer-associated fibroblasts as another polarized cell type of the tumor microenvironment. Front Oncol 2014;4:62.
64. Zhang XF, Dong M, Pan YH, et al. Expression pattern of cancer-associated fibroblast and its clinical relevance in intrahepatic cholangiocarcinoma. Hum Pathol 2017;65:92-100.
65. Chuaysri C, Thuwajit P, Paupairoj A, Chau-In S, Suthiphongchai T, Thuwajit C. Alpha-smooth muscle actin-positive fibroblasts promote biliary cell proliferation and correlate with poor survival in cholangiocarcinoma. Oncol Rep ;21:957-69.
66. Sha M, Jeong S, Qiu BJ, et al. Isolation of cancer-associated fibroblasts and its promotion to the progression of intrahepatic cholangiocarcinoma. Cancer Med 2018;7:4665-77.
67. Fabris L, Sato K, Alpini G, Strazzabosco M. The tumor microenvironment in cholangiocarcinoma progression. Hepatology 2021;73 Suppl 1:75-85.
68. Franco OE, Shaw AK, Strand DW, Hayward SW. Cancer associated fibroblasts in cancer pathogenesis. Semin Cell Dev Biol 2010;21:33-9.
69. Montori M, Scorzoni C, Argenziano ME, et al. Cancer-Associated fibroblasts in cholangiocarcinoma: current knowledge and possible implications for therapy. J Clin Med 2022;11:6498.
70. Affo S, Nair A, Brundu F, et al. Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations. Cancer Cell 2021;39:866-882.e11.
71. Zhang M, Yang H, Wan L, et al. Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma. J Hepatol 2020;73:1118-30.
72. Itou RA, Uyama N, Hirota S, et al. Immunohistochemical characterization of cancer-associated fibroblasts at the primary sites and in the metastatic lymph nodes of human intrahepatic cholangiocarcinoma. Hum Pathol 2019;83:77-89.
73. Yangngam S, Thongchot S, Pongpaibul A, et al. High level of interleukin-33 in cancer cells and cancer-associated fibroblasts correlates with good prognosis and suppressed migration in cholangiocarcinoma. J Cancer 2020;11:6571-81.
74. Miyata T, Yamashita YI, Yoshizumi T, et al. CXCL12 expression in intrahepatic cholangiocarcinoma is associated with metastasis and poor prognosis. Cancer Sci 2019;110:3197-203.
75. Gentilini A, Pastore M, Marra F, Raggi C. The role of stroma in cholangiocarcinoma: the intriguing interplay between fibroblastic component, immune cell subsets and tumor epithelium. Int J Mol Sci 2018;19:2885.
76. Cadamuro M, Nardo G, Indraccolo S, et al. Platelet-derived growth factor-D and Rho GTPases regulate recruitment of cancer-associated fibroblasts in cholangiocarcinoma. Hepatology 2013;58:1042-53.
77. Cadamuro M, Brivio S, Mertens J, et al. Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma. J Hepatol 2019;70:700-9.
78. Fingas CD, Bronk SF, Werneburg NW, et al. Myofibroblast-derived PDGF-BB promotes hedgehog survival signaling in cholangiocarcinoma cells. Hepatology 2011;54:2076-88.
79. Clapéron A, Mergey M, Aoudjehane L, et al. Hepatic myofibroblasts promote the progression of human cholangiocarcinoma through activation of epidermal growth factor receptor. Hepatology 2013;58:2001-11.
80. Nguyen MLT, Bui KC, Scholta T, et al. Targeting interleukin 6 signaling by monoclonal antibody siltuximab on cholangiocarcinoma. J Gastroenterol Hepatol 2021;36:1334-45.
81. Terashita K, Chuma M, Hatanaka Y, et al. ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma. J Clin Pathol 2016;69:593-9.
82. Qin X, Lu M, Li G, Zhou Y, Liu Z. Downregulation of tumor-derived exosomal miR-34c induces cancer-associated fibroblast activation to promote cholangiocarcinoma progress. Cancer Cell Int 2021;21:373.
83. Gentilini A, Rombouts K, Galastri S, et al. Role of the stromal-derived factor-1 (SDF-1)-CXCR4 axis in the interaction between hepatic stellate cells and cholangiocarcinoma. J Hepatol 2012;57:813-20.
84. Gentilini A, Caligiuri A, Raggi C, et al. CXCR7 contributes to the aggressive phenotype of cholangiocarcinoma cells. Biochim Biophys Acta Mol Basis Dis 2019;1865:2246-56.
85. Ohira S, Sasaki M, Harada K, et al. Possible regulation of migration of intrahepatic cholangiocarcinoma cells by interaction of CXCR4 expressed in carcinoma cells with tumor necrosis factor-alpha and stromal-derived factor-1 released in stroma. Am J Pathol 2006;168:1155-68.
86. Campbell DJ, Dumur CI, Lamour NF, Dewitt JL, Sirica AE. Novel organotypic culture model of cholangiocarcinoma progression. Hepatol Res 2012;42:1119-30.
87. Okamoto K, Tajima H, Ohta T, et al. The role of renin-angiotensin system independent angiotensin II production in progression and fibrosis of intrahepatic cholangiocarcinoma. Gan To Kagaku Ryoho 2010;37:2231-3. (in Japanese).
88. Yang X, Lin Y, Shi Y, et al. FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3-CCL2 Signaling. Cancer Res 2016;76:4124-35.
89. Lin Y, Cai Q, Chen Y, et al. CAFs shape myeloid-derived suppressor cells to promote stemness of intrahepatic cholangiocarcinoma through 5-lipoxygenase. Hepatology 2022;75:28-42.
90. Volonte D, Vyas AR, Chen C, et al. Caveolin-1 promotes the tumor suppressor properties of oncogene-induced cellular senescence. J Biol Chem 2018;293:1794-809.
91. Lan C, Kitano Y, Yamashita YI, et al. Cancer-associated fibroblast senescence and its relation with tumour-infiltrating lymphocytes and PD-L1 expressions in intrahepatic cholangiocarcinoma. Br J Cancer 2022;126:219-27.
92. Zhou SL, Dai Z, Zhou ZJ, et al. CXCL5 contributes to tumor metastasis and recurrence of intrahepatic cholangiocarcinoma by recruiting infiltrative intratumoral neutrophils. Carcinogenesis 2014;35:597-605.
93. Okabe H, Beppu T, Ueda M, et al. Identification of CXCL5/ENA-78 as a factor involved in the interaction between cholangiocarcinoma cells and cancer-associated fibroblasts. Int J Cancer 2012;131:2234-41.
94. Cadamuro M, Morton SD, Strazzabosco M, Fabris L. Unveiling the role of tumor reactive stroma in cholangiocarcinoma: an opportunity for new therapeutic strategies. Transl Gastrointest Cancer 2013;2:130-44.
95. Thelen A, Scholz A, Weichert W, et al. Tumor-associated angiogenesis and lymphangiogenesis correlate with progression of intrahepatic cholangiocarcinoma. Am J Gastroenterol 2010;105:1123-32.
96. Semela D, Das A, Langer D, Kang N, Leof E, Shah V. Platelet-derived growth factor signaling through ephrin-b2 regulates hepatic vascular structure and function. Gastroenterology 2008;135:671-9.
97. Thabut D, Shah V. Intrahepatic angiogenesis and sinusoidal remodeling in chronic liver disease: new targets for the treatment of portal hypertension? J Hepatol 2010;53:976-80.
98. Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev 2008;22:1276-312.
99. Aoki S, Inoue K, Klein S, et al. Placental growth factor promotes tumour desmoplasia and treatment resistance in intrahepatic cholangiocarcinoma. Gut 2022;71:185-93.
100. Green CJ, Lichtlen P, Huynh NT, et al. Placenta growth factor gene expression is induced by hypoxia in fibroblasts: a central role for metal transcription factor-1. Cancer Res 2001;61:2696-703.
101. Brivio S, Cadamuro M, Strazzabosco M, Fabris L. Tumor reactive stroma in cholangiocarcinoma: the fuel behind cancer aggressiveness. World J Hepatol 2017;9:455-68.
102. Aishima S, Taguchi K, Terashi T, Matsuura S, Shimada M, Tsuneyoshi M. Tenascin expression at the invasive front is associated with poor prognosis in intrahepatic cholangiocarcinoma. Mod Pathol 2003;16:1019-27.
103. Hendaoui I, Lahmar A, Campo L, et al. Tenascin-W is a novel stromal marker in biliary tract cancers. Front Immunol 2020;11:630139.
104. Utispan K, Sonongbua J, Thuwajit P, et al. Periostin activates integrin α5β1 through a PI3K/AKT-dependent pathway in invasion of cholangiocarcinoma. Int J Oncol 2012;41:1110-8.
105. Sonongbua J, Siritungyong S, Thongchot S, et al. Periostin induces epithelial-to-mesenchymal transition via the integrin α5β1/TWIST-2 axis in cholangiocarcinoma. Oncol Rep 2020;43:1147-58.
106. Leavenworth JW, Verbinnen B, Wang Q, Shen E, Cantor H. Intracellular osteopontin regulates homeostasis and function of natural killer cells. Proc Natl Acad Sci U S A 2015;112:494-9.
107. Klement JD, Paschall AV, Redd PS, et al. An osteopontin/CD44 immune checkpoint controls CD8+ T cell activation and tumor immune evasion. J Clin Invest 2018;128:5549-60.
108. Sulpice L, Rayar M, Desille M, et al. Molecular profiling of stroma identifies osteopontin as an independent predictor of poor prognosis in intrahepatic cholangiocarcinoma. Hepatology 2013;58:1992-2000.
109. Zheng Y, Zhou C, Yu XX, et al. Osteopontin promotes metastasis of intrahepatic cholangiocarcinoma through recruiting MAPK1 and mediating Ser675 phosphorylation of β-Catenin. Cell Death Dis 2018;9:179.
110. Jing CY, Fu YP, Zhou C, et al. Hepatic stellate cells promote intrahepatic cholangiocarcinoma progression via NR4A2/osteopontin/Wnt signaling axis. Oncogene 2021;40:2910-22.
111. Rimassa L, Personeni N, Aghemo A, Lleo A. The immune milieu of cholangiocarcinoma: From molecular pathogenesis to precision medicine. J Autoimmun 2019;100:17-26.
112. Subimerb C, Pinlaor S, Khuntikeo N, et al. Tissue invasive macrophage density is correlated with prognosis in cholangiocarcinoma. Mol Med Rep 2010;3:597-605.
113. Paillet J, Kroemer G, Pol JG. Immune contexture of cholangiocarcinoma. Curr Opin Gastroenterol 2020;36:70-6.
114. Szulc-kielbik I, Kielbik M. Tumor-Associated Macrophages: reasons to be cheerful, reasons to be fearful. In: Klink M, Szulc-kielbik I, editors. Interaction of immune and cancer cells. Cham: Springer International Publishing; 2022. pp. 107-40.
115. Pathria P, Louis TL, Varner JA. Targeting tumor-associated macrophages in cancer. Trends Immunol 2019;40:310-27.
116. Høgdall D, Lewinska M, Andersen JB. Desmoplastic tumor microenvironment and immunotherapy in cholangiocarcinoma. Trends Cancer 2018;4:239-55.
117. Debebe A, Medina V, Chen CY, et al. Wnt/β-catenin activation and macrophage induction during liver cancer development following steatosis. Oncogene 2017;36:6020-9.
118. Loilome W, Bungkanjana P, Techasen A, et al. Activated macrophages promote Wnt/β-catenin signaling in cholangiocarcinoma cells. Tumour Biol 2014;35:5357-67.
119. Zhou M, Wang C, Lu S, et al. Tumor-associated macrophages in cholangiocarcinoma: complex interplay and potential therapeutic target. EBioMedicine 2021;67:103375.
120. Boulter L, Guest RV, Kendall TJ, et al. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J Clin Invest 2015;125:1269-85.
121. Li X, Chen L, Peng X, Zhan X. Progress of tumor-associated macrophages in the epithelial-mesenchymal transition of tumor. Front Oncol 2022;12:911410.
122. Vakili-Ghartavol R, Mombeiny R, Salmaninejad A, et al. Tumor-associated macrophages and epithelial-mesenchymal transition in cancer: nanotechnology comes into view. J Cell Physiol 2018;233:9223-36.
123. Techasen A, Loilome W, Namwat N, Dokduang H, Jongthawin J, Yongvanit P. Cytokines released from activated human macrophages induce epithelial mesenchymal transition markers of cholangiocarcinoma cells. Asian Pac J Cancer Prev 2012;13 Suppl:115-8.
124. Thanee M, Loilome W, Techasen A, et al. Quantitative changes in tumor-associated M2 macrophages characterize cholangiocarcinoma and their association with metastasis. Asian Pac J Cancer Prev 2015;16:3043-50.
125. Cadamuro M, Stecca T, Brivio S, et al. The deleterious interplay between tumor epithelia and stroma in cholangiocarcinoma. Biochim Biophys Acta Mol Basis Dis 2018;1864:1435-43.
126. Techasen A, Namwat N, Loilome W, et al. Tumor necrosis factor-α modulates epithelial mesenchymal transition mediators ZEB2 and S100A4 to promote cholangiocarcinoma progression. J Hepatobiliary Pancreat Sci 2014;21:703-11.
127. Techasen A, Namwat N, Loilome W, et al. Tumor necrosis factor-α (TNF-α) stimulates the epithelial-mesenchymal transition regulator Snail in cholangiocarcinoma. Med Oncol 2012;29:3083-91.
128. Mariotti V, Fiorotto R, Cadamuro M, Fabris L, Strazzabosco M. New insights on the role of vascular endothelial growth factor in biliary pathophysiology. JHEP Rep 2021;3:100251.
129. Subimerb C, Pinlaor S, Lulitanond V, et al. Circulating CD14+CD16+ monocyte levels predict tissue invasive character of cholangiocarcinoma. Clin Exp Immunol 2010;161:471-9.
130. Hasita H, Komohara Y, Okabe H, et al. Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma. Cancer Sci 2010;101:1913-9.
131. Ruffolo LI, Jackson KM, Kuhlers PC, et al. GM-CSF drives myelopoiesis, recruitment and polarisation of tumour-associated macrophages in cholangiocarcinoma and systemic blockade facilitates antitumour immunity. Gut 2022;71:1386-98.
132. Walter D, Herrmann E, Schnitzbauer AA, et al. PD-L1 expression in extrahepatic cholangiocarcinoma. Histopathology 2017;71:383-92.
133. Gani F, Nagarajan N, Kim Y, et al. Program death 1 immune checkpoint and tumor microenvironment: implications for patients with intrahepatic cholangiocarcinoma. Ann Surg Oncol 2016;23:2610-7.
134. Kitano Y, Yamashita YI, Nakao Y, et al. Clinical significance of PD-L1 expression in both cancer and stroma cells of cholangiocarcinoma patients. Ann Surg Oncol 2020;27:599-607.
135. Hutchinson JH, Rowbottom MW, Lonergan D, et al. Small molecule lysyl oxidase-like 2 (LOXL2) inhibitors: the identification of an inhibitor selective for LOXL2 over LOX. ACS Med Chem Lett 2017;8:423-7.
136. Wong CC, Tse AP, Huang YP, et al. Lysyl oxidase-like 2 is critical to tumor microenvironment and metastatic niche formation in hepatocellular carcinoma. Hepatology 2014;60:1645-58.
137. Kato M, Kurozumi A, Goto Y, et al. Regulation of metastasis-promoting LOXL2 gene expression by antitumor microRNAs in prostate cancer. J Hum Genet 2017;62:123-32.
138. Xie L, Dai BM, Jiang ZQ. Comparative study of outer envelope protein and LPS of five strains of leptospires by SDS-PAGE and 2D-PAGE. Hua Xi Yi Ke Da Xue Xue Bao 1989;20:361-5.
139. Mertens JC, Fingas CD, Christensen JD, et al. Therapeutic effects of deleting cancer-associated fibroblasts in cholangiocarcinoma. Cancer Res 2013;73:897-907.
140. Yamanaka T, Harimoto N, Yokobori T, et al. Nintedanib inhibits intrahepatic cholangiocarcinoma aggressiveness via suppression of cytokines extracted from activated cancer-associated fibroblasts. Br J Cancer 2020;122:986-94.
141. Thongchot S, Ferraresi A, Vidoni C, et al. Resveratrol interrupts the pro-invasive communication between cancer associated fibroblasts and cholangiocarcinoma cells. Cancer Lett 2018;430:160-71.
142. Razumilava N, Gradilone SA, Smoot RL, et al. Non-canonical Hedgehog signaling contributes to chemotaxis in cholangiocarcinoma. J Hepatol 2014;60:599-605.
143. Riedlinger D, Bahra M, Boas-Knoop s, et al. Hedgehog pathway as a potential treatment target in human cholangiocarcinoma. J Hepatobiliary Pancreat Sci 2014;21:607-15.
144. Kiesslich T, Mayr C, Wachter J, et al. Activated hedgehog pathway is a potential target for pharmacological intervention in biliary tract cancer. Mol Cell Biochem 2014;396:257-68.
145. Anichini G, Carrassa L, Stecca B, Marra F, Raggi C. The role of the hedgehog pathway in cholangiocarcinoma. Cancers 2021;13:4774.
146. Thongchot S, Vidoni C, Ferraresi A, et al. Cancer-Associated fibroblast-derived il-6 determines unfavorable prognosis in cholangiocarcinoma by affecting autophagy-associated chemoresponse. Cancers 2021;13:2134.
147. Nicolás-Boluda A, Vaquero J, Laurent G, et al. Photothermal depletion of cancer-associated fibroblasts normalizes tumor stiffness in desmoplastic cholangiocarcinoma. ACS Nano 2020;14:5738-53.
148. Cheng K, Cai N, Zhu J, Yang X, Liang H, Zhang W. Tumor-associated macrophages in liver cancer: from mechanisms to therapy. Cancer Commun 2022;42:1112-40.
149. Dwyer BJ, Jarman EJ, Gogoi-Tiwari J, et al. TWEAK/Fn14 signalling promotes cholangiocarcinoma niche formation and progression. J Hepatol 2021;74:860-72.
150. Yang T, Deng Z, Xu L, et al. Macrophages-aPKCɩ-CCL5 feedback loop modulates the progression and chemoresistance in cholangiocarcinoma. J Exp Clin Cancer Res 2022;41:23.
151. Diggs LP, Ruf B, Ma C, et al. CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma. J Hepatol 2021;74:1145-54.
