AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.2911
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RESEARCH ARTICLE

Bioprinting native-like 3D micro breast cancer tissues utilizing existing cancer cell lines

Brian E. Grottkau1,2* ,  Zhixin Hui1 ,  Yonggang Pang1*
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1 The Laboratory for Therapeutic 3D Bioprinting, Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
2 Department of Orthopedics, University of Miami Medical Center and Jackson Memorial Hospital, Miami, FL 33136, USA
IJB 2024, 10(3), 2911 https://doi.org/10.36922/ijb.2911
Submitted: 9 February 2024 | Accepted: 3 April 2024 | Published: 13 June 2024
© 2024 by the Author(s).. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

3D cancer cell models provide a more accurate representation of in vivo conditions than traditional 2D cultures. Many cancer cell lines, while stable and extensively characterized in 2D environments, often underperform compared to primary cells in 3D models due to the inherent resource constraints and variability of the latter. To bridge this gap and harness the full potential of established cancer cell lines, we adopted the innovative direct volumetric drop-on-demand (DVDOD) bioprinting methodology that we have developed previously, leading to the inception of printed micro-cancer tissues (PMCaTs). Our method, notable for its bioink droplet scattering technique, enables the generation of intricate features within a droplet, allowing for the creation of typical architectures of breast cancer tissue. We created PMCaTs that captured the essence of micro breast cancer tissues, from native-like ductal structures and cancer nests to the intricate cancer microenvironment. This encompasses elements like cancer-associated fibroblasts, detailed microvasculature, and regions marked by both intensive proliferation and hypoxia. These bioprinted models demonstrate long-term viability and are instrumental for diverse research areas—from exploring cancer growth dynamics and hypoxia-induced behaviors to investigating the nuances of microvasculature, drug penetration capabilities, immune responses, metastatic trends, and clinical drug response predictions. Ultimately, our groundbreaking DVDOD bioprinting technique holds the promise of reshaping the landscape of cancer research, introducing advanced in vitro models poised to transform therapeutic exploration.

 

Keywords
Bioprinting
Direct volumetric drop-on-demand
3D micro breast cancer tissues
Native-like
Cancer cell lines
3D models
Funding
This project was funded by the Peabody Foundation, Inc., the Anthony and Constance Franchi Fund for Pediatric Orthopaedics, the Massachusetts General Hospital Department of Orthopaedic Surgery and University of Miami Medical Center and Jackson Memorial Hospital Department of Orthopaedics.
Conflict of interest
Dr. Brian E. Grottkau is the founder of 3D Biotherapeutics, Inc. Dr. Yonggang Pang and Zhixin Hui declare no conflict of interest.
References
  1. Hidalgo M, Amant F, Biankin AV, et al. Patient-derived xenograft models: an emerging platform for translational cancer research. Cancer Discov. 2014;4(9):998–1013. doi: 10.1158/2159-8290.CD-14-0001
  2. Langhans SA. Three-dimensional in vitro cell culture models in drug discovery and drug repositioning. Front Pharmacol. 2018;9:6. doi: 10.3389/fphar.2018.00006
  3. Nusinow DP, Szpyt J, Ghandi M, et al. Quantitative proteomics of the cancer cell line encyclopedia. Cell. 2020;180(2):387–402.e16. doi: 10.1016/j.cell.2019.12.023
  4. Cancer Therapeutics Response Portal. https://portals. broadinstitute.org/ctrp.v2.1/. Accessed August 13, 2023.
  5. Dai X, Cheng H, Bai Z, Li J. Breast cancer cell line classification and its relevance with breast tumor subtyping. J Cancer. 2017;8(16):3131–3141. doi: 10.7150/jca.18457
  6. Li Y, Kilian KA. Bridging the gap: from 2D cell culture to 3D microengineered extracellular matrices. Adv Healthc Mater. 2015;4(18):2780–2796.
  7. Egeblad M, Nakasone ES, Werb Z. Tumors as organs: complex tissues that interface with the entire organism. Dev Cell. 2010;18(6):884–901. doi: 10.1016/j.devcel.2010.05.012
  8. Sachs N, Clevers H. Organoid cultures for the analysis of cancer phenotypes. Curr Opin Genet Dev. 2014;24:68–73. doi: 10.1016/j.gde.2013.11.012
  9. Clevers H. Modeling development and disease with organoids. Cell. 2016;165(7):1586–1597. doi: 10.1016/j.cell.2016.05.082
  10. Ramesh S, Harrysson OLA, Rao PK, et al. Extrusion bioprinting: recent progress, challenges, and future opportunities. Bioprinting. 2021;21:e00116. doi: 10.1016/j.bprint.2020.e00116
  11. Chartrain NA, Williams CB, Whittington AR. A review on fabricating tissue scaffolds using vat photopolymerization. Acta Biomater. 2018;74:90–111. doi: 10.1016/j.actbio.2018.05.010
  12. Ng WL, Shkolnikov V. Optimizing cell deposition for inkjet-based bioprinting. IJB. 2024;0(0):2135. doi: 10.36922/ijb.2135
  13. Grottkau BE, Hui Z, Pang Y. A novel 3D bioprinter using direct-volumetric drop-on-demand technology for fabricating micro-tissues and drug-delivery. IJMS. 2020;21(10):3482. doi: 10.3390/ijms21103482
  14. Grottkau BE, Hui Z, Pang Y. Cellular patterning alone using bioprinting regenerates articular cartilage through native-like cartilagenesis. Research Square. 2023. doi: 10.21203/rs.3.rs-3380357/v1
  15. Bashar MA, Begam N. Breast cancer surpasses lung cancer as the most commonly diagnosed cancer worldwide. Indian J Cancer. 2022;59(3):438–439. doi: 10.4103/ijc.IJC_83_21
  16. Arnold M, Morgan E, Rumgay H, et al. Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast. 2022;66:15–23. doi: 10.1016/j.breast.2022.08.010
  17. Pang Y, Ucuzian AA, Matsumura A, et al. The temporal and spatial dynamics of microscale collagen scaffold remodeling by smooth muscle cells. Biomaterials. 2009;30(11): 2023–2031. doi: 10.1016/j.biomaterials.2008.12.064
  18. Chen Y, McAndrews KM, Kalluri R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat Rev Clin Oncol. 2021;18(12):792–804. doi: 10.1038/s41571-021-00546-5
  19. Weiss L, Orr FW, Honn KV. Interactions of cancer cells with the microvasculature during metastasis. FASEB J. 1988;2(1):12–21. doi: 10.1096/fasebj.2.1.3275560
  20. Strzyz P. Cancer biology: hypoxia as an off switch for gene expression. Nat Rev Mol Cell Biol. 2016;17(10):610. doi: 10.1038/nrm.2016.119
  21. Koshiji M, Kageyama Y, Pete EA, Horikawa I, Barrett JC, Huang LE. HIF-1α induces cell cycle arrest by functionally counteracting Myc. EMBO J. 2004;23(9):1949–1956. doi: 10.1038/sj.emboj.7600196
  22. Hubbi ME, Kshitiz, Gilkes DM, et al. A Nontranscriptional Role for HIF-1α as a Direct Inhibitor of DNA Replication. Sci Signal. 2013;6(262):ra10. doi: 10.1126/scisignal.2003417
  23. Zhang Y, Zhang H, Wang M, et al. Hypoxia in breast cancer—scientific translation to therapeutic and diagnostic clinical applications. Front Oncol. 2021;11:652266. doi: 10.3389/fonc.2021.652266
  24. Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discov. 2019;18(2): 99–115. doi: 10.1038/s41573-018-0004-1
  25. Pepin F, Bertos N, Laferrière J, et al. Gene-expression profiling of microdissected breast cancer microvasculature identifies distinct tumor vascular subtypes. Breast Cancer Res. 2012;14(4):R120. doi: 10.1186/bcr3246
  26. Frentzas S, Simoneau E, Bridgeman VL, et al. Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases. Nat Med. 2016;22(11):1294–1302. doi: 10.1038/nm.4197
  27. Jain RK. Lessons from multidisciplinary translational trials on anti-angiogenic therapy of cancer. Nat Rev Cancer. 2008;8(4):309–316. doi: 10.1038/nrc2346
  28. Yu M, Tannock IF. Targeting tumor architecture to favor drug penetration: a new weapon to combat chemoresistance in pancreatic cancer? Cancer Cell. 2012;21(3):327–329. doi: 10.1016/j.ccr.2012.03.002
  29. Wang C, Chen S, Wang Y, et al. Lipase-triggered water-responsive “Pandora’s Box” for cancer therapy: toward induced neighboring effect and enhanced drug penetration. Adv Mater. 2018;30(14):e1706407. doi: 10.1002/adma.201706407
  30. Di Cosimo S. Advancing immunotherapy for early-stage triple-negative breast cancer. Lancet. 2020;396(10257):1046–1048. doi: 10.1016/S0140-6736(20)31962-0
  31. Riley RS, June CH, Langer R, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov. 2019;18(3):175–196. doi: 10.1038/s41573-018-0006-z
  32. Becker JC, Andersen MH, Schrama D, Thor Straten P. Immune-suppressive properties of the tumor microenvironment. Cancer Immunol Immunother. 2013;62(7):1137–1148. doi: 10.1007/s00262-013-1434-6
  33. Wirtz D, Konstantopoulos K, Searson PC. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer. 2011;11(7):512–522. doi: 10.1038/nrc3080
  34. Murphy PM. Chemokines and the molecular basis of cancer metastasis. N Engl J Med. 2001;345(11):833–835. doi: 10.1056/NEJM200109133451113
  35. Zardavas D, Maetens M, Irrthum A, et al. The AURORA initiative for metastatic breast cancer. Br J Cancer. 2014;111(10):1881–1887. doi: 10.1038/bjc.2014.341
  36. Haddad TC, Suman VJ, D’Assoro AB, et al. Evaluation of alisertib alone or combined with fulvestrant in patients with endocrine-resistant advanced breast cancer: the Phase 2 TBCRC041 randomized clinical trial. JAMA Oncol. 2023;9(6):815–824. doi: 10.1001/jamaoncol.2022.7949
  37. Melichar B, Adenis A, Lockhart AC, et al. Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study. Lancet Oncol. 2015;16(4): 395–405. doi: 10.1016/S1470-2045(15)70051-3
  38. Li JP, Yang YX, Liu QL, et al. The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells. Drug Des Devel Ther. 2015;9:1627–1652. doi: 10.2147/DDDT.S75378

 




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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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