Multicellular tumor spheroid model to study the multifaceted role of tumor-associated macrophages in PDAC

Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660.

Article  PubMed  Google Scholar 

Ferlay J, Partensky C, Bray F. More deaths from pancreatic cancer than breast cancer in the EU by 2017. Acta Oncol. 2016;55(9–10):1158–60. https://doi.org/10.1080/0284186X.2016.1197419.

Article  CAS  PubMed  Google Scholar 

Damanakis AI, Gebauer F, Popp F, Bruns C. The hallmarks of pancreatic cancer. In: Søreide K, Stättner S, editors. Textbook of Pancreatic Cancer: Principles and Practice of Surgical Oncology. Cham: Springer International Publishing; 2021;189–201.

Geng X, Chen H, Zhao L, et al. Cancer-associated fibroblast (CAF) heterogeneity and targeting therapy of CAFs in pancreatic cancer. Front Cell Dev Biol. 2021;9:655152. https://doi.org/10.3389/fcell.2021.655152.

Article  PubMed  PubMed Central  Google Scholar 

Dougan SK. The pancreatic cancer microenvironment. Cancer J. 2017;23(6).

Erkan M, Kurtoglu M, Kleeff J. The role of hypoxia in pancreatic cancer: A potential therapeutic target? Expert Rev Gastroenterol Hepatol. 2016;10(3):301–16. https://doi.org/10.1586/17474124.2016.1117386.

Article  CAS  PubMed  Google Scholar 

Orth M, Metzger P, Gerum S, et al. Pancreatic ductal adenocarcinoma: Biological hallmarks, current status, and future perspectives of combined modality treatment approaches. Radiat Oncol. 2019;14(1):141. https://doi.org/10.1186/s13014-019-1345-6.

Article  PubMed  PubMed Central  Google Scholar 

Kurahara H, Shinchi H, Mataki Y, et al. Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. J Surg Res. 2011;167(2):e211–9. https://doi.org/10.1016/j.jss.2009.05.026.

Article  PubMed  Google Scholar 

Yu M, Guan R, Hong W, et al. Prognostic value of tumor-associated macrophages in pancreatic cancer: A meta-analysis. Cancer Manag Res. 2019;11:4041–58. https://doi.org/10.2147/CMAR.S196951.

Article  PubMed  PubMed Central  Google Scholar 

Cassetta L, Pollard JW. Targeting macrophages: Therapeutic approaches in cancer. Nat Rev Drug Discov. 2018;17(12):887–904. https://doi.org/10.1038/nrd.2018.169.

Article  CAS  PubMed  Google Scholar 

Noy R, Pollard JW. Tumor-associated macrophages: From mechanisms to therapy. Immunity. 2014;41(1):49–61. https://doi.org/10.1016/j.immuni.2014.06.010.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141(1):39–51. https://doi.org/10.1016/j.cell.2010.03.014.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Franklin RA, Liao W, Sarkar A, et al. The cellular and molecular origin of tumor-associated macrophages. Science. 2014;344(6186):921–5. https://doi.org/10.1126/science.1252510.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhu Y, Herndon JM, Sojka DK, et al. Tissue-resident macrophages in pancreatic ductal adenocarcinoma originate from embryonic hematopoiesis and promote tumor progression. Immunity. 2017;47(2):323-38.e6. https://doi.org/10.1016/j.immuni.2017.07.014.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu K, Lin K, Li X et al. Redefining tumor-associated macrophage subpopulations and functions in the tumor microenvironment. Front Immunol. 2020;11(1731). https://doi.org/10.3389/fimmu.2020.01731.

Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol. 2020;15:123–47. https://doi.org/10.1146/annurev-pathmechdis-012418-012718.

Article  CAS  PubMed  Google Scholar 

Blériot C, Chakarov S, Ginhoux F. Determinants of resident tissue macrophage identity and function. Immunity. 2020;52(6):957–70. https://doi.org/10.1016/j.immuni.2020.05.014.

Article  CAS  PubMed  Google Scholar 

Daley D, Mani VR, Mohan N, et al. Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance. Nat Med. 2017;23(5):556–67. https://doi.org/10.1038/nm.4314.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martinez-Bosch N, Vinaixa J, Navarro P. Immune evasion in pancreatic cancer: From mechanisms to therapy. Cancers. 2018;10(1). https://doi.org/10.3390/cancers10010006.

Sun L, Zhang X, Song Q, et al. IGFBP2 promotes tumor progression by inducing alternative polarization of macrophages in pancreatic ductal adenocarcinoma through the STAT3 pathway. Cancer Lett. 2021;500:132–46. https://doi.org/10.1016/j.canlet.2020.12.008.

Article  CAS  PubMed  Google Scholar 

Tekin C, Aberson HL, Waasdorp C, et al. Macrophage-secreted MMP9 induces mesenchymal transition in pancreatic cancer cells via PAR1 activation. Cell Oncol. 2020;43(6):1161–74. https://doi.org/10.1007/s13402-020-00549-x.

Article  CAS  Google Scholar 

Xiong C, Zhu Y, Xue M et al. Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition. Aging. 2021;13(3):3386–404. https://doi.org/10.18632/aging.202264.

Bulle A, Dekervel J, Deschuttere L, et al. Gemcitabine recruits M2-type tumor-associated macrophages into the stroma of pancreatic cancer. Transl Oncol. 2020;13(3):100743. https://doi.org/10.1016/j.tranon.2020.01.004.

Article  PubMed  PubMed Central  Google Scholar 

D’Errico G, Alonso-Nocelo M, Vallespinos M, et al. Tumor-associated macrophage-secreted 14–3-3ζ signals via AXL to promote pancreatic cancer chemoresistance. Oncogene. 2019;38(27):5469–85. https://doi.org/10.1038/s41388-019-0803-9.

Article  CAS  PubMed  Google Scholar 

Halbrook CJ, Pontious C, Kovalenko I, et al. Macrophage-released pyrimidines inhibit gemcitabine therapy in pancreatic cancer. Cell Metab. 2019;29(6):1390-9.e6. https://doi.org/10.1016/j.cmet.2019.02.001.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Anfray C, Ummarino A, Andón FT, Allavena P. Current strategies to target tumor-associated-macrophages to improve anti-tumor immune responses. Cells. 2019;9(1). https://doi.org/10.3390/cells9010046.

Cheng N, Bai X, Shu Y, Ahmad O, Shen P. Targeting tumor-associated macrophages as an antitumor strategy. Biochem Pharmacol. 2021;183:114354. https://doi.org/10.1016/j.bcp.2020.114354.

Article  CAS  PubMed  Google Scholar 

Zhou K, Cheng T, Zhan J, et al. Targeting tumor-associated macrophages in the tumor microenvironment. Oncol Lett. 2020;20(5):234. https://doi.org/10.3892/ol.2020.12097.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lazzari G, Couvreur P, Mura S. Multicellular tumor spheroids: A relevant 3D model for the in vitro preclinical investigation of polymer nanomedicines. Polym Chem. 2017;8(34):4947–69. https://doi.org/10.1039/C7PY00559H.

Article  CAS  Google Scholar 

Lu H, Stenzel MH. Multicellular tumor spheroids (MCTS) as a 3D in vitro evaluation tool of nanoparticles. Small. 2018;14(13):e1702858. https://doi.org/10.1002/smll.201702858.

Article  CAS  PubMed  Google Scholar 

Gundel B, Liu X, Lohr M, Heuchel R. Pancreatic ductal adenocarcinoma: Preclinical in vitro and ex vivo models. Front Cell Dev Biol. 2021;9:741162. https://doi.org/10.3389/fcell.2021.741162.

Article  PubMed  PubMed Central  Google Scholar 

Tanaka HY, Kurihara T, Nakazawa T, et al. Heterotypic 3D pancreatic cancer model with tunable proportion of fibrotic elements. Biomaterials. 2020;251:120077. https://doi.org/10.1016/j.biomaterials.2020.120077.

Article  CAS  PubMed  Google Scholar 

Ware MJ, Keshishian V, Law JJ, et al. Generation of an in vitro 3D PDAC stroma rich spheroid model. Biomaterials. 2016;108:129–42. https://doi.org/10.1016/j.biomaterials.2016.08.041.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lazzari G, Nicolas V, Matsusaki M, et al. Multicellular spheroid based on a triple co-culture: A novel 3D model to mimic pancreatic tumor complexity. Acta Biomater. 2018;78:296–307. https://doi.org/10.1016/j.actbio.2018.08.008.

Article  CAS  PubMed  Google Scholar 

Giustarini G, Teng G, Pavesi A, Adriani G. Characterization of 3D heterocellular spheroids of pancreatic ductal adenocarcinoma for the study of cell interactions in the tumor immune microenvironment. Front Oncol. 2023;13:1156769. https://doi.org/10.3389/fonc.2023.1156769.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sant S, Johnston PA. The production of 3D tumor spheroids for cancer drug discovery. Drug Discov Today Technol. 2017;23:27–36. https://doi.org/10.1016/j.ddtec.2017.03.002.

Article  PubMed  PubMed Central  Google Scholar 

Tevis KM, Cecchi RJ, Colson YL, Grinstaff MW. Mimicking the tumor microenvironment to regulate macrophage phenotype and assessing chemotherapeutic efficacy in embedded cancer cell/macrophage spheroid models. Acta Biomater. 2017;50:271–9. https://doi.org/10.1016/j.actbio.2016.12.037.

Article  CAS  PubMed  Google Scholar 

Nunes AS, Barros AS, Costa EC, Moreira AF, Correia IJ. 3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs. Biotechnol Bioeng. 2019;116(1):206–26.

Comments (0)

No login
gif