Skip to main content

3D In Vitro Model for Breast Cancer Research Using Magnetic Levitation and Bioprinting Method

  • Protocol
  • First Online:
Breast Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1406))

Abstract

Tumor microenvironment composition and architecture are known as a major factor in orchestrating the tumor growth and its response to various therapies. In this context, in vivo studies are necessary to evaluate the responses. However, while tumor cells can be of human origin, tumor microenvironment in the in vivo models is host-based. On the other hand, in vitro studies in a flat monoculture of tumor cells (the most frequently used in vitro tumor model) are unable to recapitulate the complexity of tumor microenvironment. Three-dimensional (3D) in vitro cell cultures of tumor cells have been proven to be an important experimental tool in understanding mechanisms of tumor growth, response to therapeutics, and transport of nutrients/drugs. We have recently described a novel tool to create 3D co-cultures of tumor cells and cells in the tumor microenvironment. Our method utilizes magnetic manipulation/levitation of the specific ratios of tumor cells and cells in the tumor microenvironment (from human or animal origin) aiding in the formation of tumor spheres with defined cellular composition and density, as quickly as within 24 h. This chapter describes the experimental protocols developed to model the 3D structure of the cancer environment using the above method.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Vinci M, Gowan S, Boxall F, Patterson L, Zimmermann M, Court W, Lomas C, Mendiola M, Hardisson D, Eccles SA (2012) Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation. BMC Biol 10:29. doi:10.1186/1741-7007-10-29

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Yamada KM, Cukierman E (2007) Modeling tissue morphogenesis and cancer in 3D. Cell 130(4):601–610. doi:10.1016/j.cell.2007.08.006

    Article  PubMed  CAS  Google Scholar 

  3. Lukashev ME, Werb Z (1998) ECM signalling: orchestrating cell behaviour and misbehaviour. Trends Cell Biol 8(11):437–441. doi:10.1016/s0962-8924(98)01362-2

    Article  PubMed  CAS  Google Scholar 

  4. Talukdar S, Mandal M, Hutmacher DW, Russell PJ, Soekmadji C, Kundu SC (2011) Engineered silk fibroin protein 3D matrices for in vitro tumor model. Biomaterials 32(8):2149–2159. doi:10.1016/j.biomaterials.2010.11.052

    Article  PubMed  CAS  Google Scholar 

  5. De Kruijf EM, Van Nes JGH, Van De Velde CJH, Putter H, Smit VTHBM, Liefers GJ, Kuppen PJK, Tollenaar RAEM, Mesker WE (2011) Tumor-stroma ratio in the primary tumor is a prognostic factor in early breast cancer patients, especially in triple-negative carcinoma patients. Breast Cancer Res Treat 125(3):687–696. doi:10.1007/s10549-010-0855-6

    Article  PubMed  Google Scholar 

  6. Lu P, Weaver VM, Werb Z (2012) The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol 196(4):395–406. doi:10.1083/jcb.201102147

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Dittmer J, Leyh B (2015) The impact of tumor stroma on drug response in breast cancer. Semin Cancer Biol 31:3–15. doi:10.1016/j.semcancer.2014.05.006

    Article  PubMed  CAS  Google Scholar 

  8. McMillin DW, Negri JM, Mitsiades CS (2013) The role of tumour-stromal interactions in modifying drug response: challenges and opportunities. Nat Rev Drug Discov 12(3):217–228. doi:10.1038/nrd3870

    Article  PubMed  CAS  Google Scholar 

  9. Watt FM, Huck WTS (2013) Role of the extracellular matrix in regulating stem cell fate. Nat Rev Mol Cell Biol 14(8):467–473. doi:10.1038/nrm3620

    Article  PubMed  CAS  Google Scholar 

  10. Jaganathan H, Gage J, Leonard F, Srinivasan S, Souza GR, Dave B, Godin B (2014) Three-dimensional in vitro co-culture model of breast tumor using magnetic levitation. Sci Rep 4:6468. doi:10.1038/srep06468

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Downey CL, Simpkins SA, White J, Holliday DL, Jones JL, Jordan LB, Kulka J, Pollock S, Rajan SS, Thygesen HH, Hanby AM, Speirs V (2014) The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer. Br J Cancer 110(7):1744–1747. doi:10.1038/bjc.2014.69

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Haisler WL, Timm DM, Gage JA, Tseng H, Killian TC, Souza GR (2013) Three-dimensional cell culturing by magnetic levitation. Nat Protoc 8(10):1940–1949. doi:10.1038/nprot.2013.125

    Article  PubMed  CAS  Google Scholar 

  13. Souza GR, Molina JR, Raphael RM, Ozawa MG, Stark DJ, Levin CS, Bronk LF, Ananta JS, Mandelin J, Georgescu MM, Bankson JA, Gelovani JG, Killian TC, Arap W, Pasqualini R (2010) Three-dimensional tissue culture based on magnetic cell levitation. Nat Nanotechnol 5(4):291–296. doi:10.1038/nnano.2010.23

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Daquinag AC, Souza GR, Kolonin MG (2013) Adipose tissue engineering in three-dimensional levitation tissue culture system based on magnetic nanoparticles. Tissue Eng Part C Methods 19(5):336–344

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Tseng H, Gage JA, Raphael RM, Moore RH, Killian TC, Grande-Allen KJ, Souza GR (2013) Assembly of a three-dimensional multitype bronchiole coculture model using magnetic levitation. Tissue Eng Part C Methods 19(9):665–675. doi:10.1089/ten.tec.2012.0157

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge Nano3D Biosciences Inc for technical support and Susan G. Komen PDF12229449 Award, NIH U54CA143837, and NIH 1U54CA151668-01 for the financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Biana Godin Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Leonard, F., Godin, B. (2016). 3D In Vitro Model for Breast Cancer Research Using Magnetic Levitation and Bioprinting Method. In: Cao, J. (eds) Breast Cancer. Methods in Molecular Biology, vol 1406. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3444-7_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-3444-7_21

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3442-3

  • Online ISBN: 978-1-4939-3444-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics