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Cited by 1353D Printing in Biomedical ResearchHydrogels: synthesis, properties, applicationsCellular Mechanics and Interactions

Development of an in Vitro 3D Tumor Model to Study Therapeutic Efficiency of an Anticancer Drug

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Shin, Crystal S., Kwak, Bongseop, Han, Bumsoo, Park, Kinam·2013·Molecular Pharmaceutics
DOI 10.1021/mp300595aPMC PMC3880422
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Abstract

The importance and advantages of three-dimensional (3D) cell cultures have been well-recognized. Tumor cells cultured in a 3D culture system as multicellular tumor spheroids (MTS) can bridge the gap between in vitro and in vivo anticancer drug evaluations. An in vitro 3D tumor model capable of providing close predictions of in vivo drug efficacy will enhance our understanding, design, and development of better drug delivery systems. Here, we developed an in vitro 3D tumor model by adapting the hydrogel template strategy to culture uniformly sized spheroids in a hydrogel scaffold containing microwells. The in vitro 3D tumor model was to closely simulate an in vivo solid tumor and its microenvironment for evaluation of anticancer drug delivery systems. MTS cultured in the hydrogel scaffold are used to examine the effect of culture conditions on the drug responses. Free MTS released from the scaffold are transferred to a microfluidic channel to simulate a dynamic in vivo microenvironment. The in vitro 3D tumor model that mimics biologically relevant parameters of in vivo microenvironments such as cell-cell and cell-ECM interactions, and a dynamic environment would be a valuable device to examine efficiency of anticancer drug and targeting specificity. These models have potential to provide in vivo correlated information to improve and optimize drug delivery systems for an effective chemotherapy.

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  1. [1]Owen SC Shoichet MS Design of three-dimensional biomimetic scaffolds J. Biomed. Mater. Res. Part A 2010 94 4 1321 1331 20597126
  2. [2]Abbott A Cell culture: biology’s new dimension Nature 2003 424 6951 870 872 12931155
  3. [3]Fischbach C Chen R Matsumoto T Schmelzle T Brugge JS Polverini PJ Mooney DJ Engineering tumors with 3D scaffolds Nat. Methods 2007 4 10 855 860 17767164
  4. [4]Feder-Mengus C Ghosh S Reschner A Martin I Spagnoli GC New dimensions in tumor immunology: what does 3D culture reveal? Trends Mol. Med 2008 14 8 333 340 18614399
  5. [5]Hamilton G Multicellular spheroids as an in vitro tumor model Cancer Lett 1998 131 1 29 34 9839617
  6. [6]Del Duca D Werbowetski T Del Maestro RF Spheroid Preparation from Hanging Drops: Characterization of a Model of Brain Tumor Invasion J. Neuro-Oncology 2004 67 3 295 303 15164985
  7. [7]Drasdo D Hohme S A single-cell-based model of tumor growth in vitro: monolayers and spheroids Phys. Biol 2005 2 3 133 147 16224119
  8. [8]Goodman TT Ng CP Pun SH 3-D tissue culture systems for the evaluation and optimization of nanoparticle-based drug carriers Bioconjugate Chem 2008 19 10 1951 1959 PMC2652657 18788773
  9. [9]Kunz-Schughart LA Kreutz M Knuechel R Multicellular spheroids: a three-dimensional in vitro culture system to study tumour biology Int. J. Exp. Pathology 1998 79 1 1 23 PMC3219428 9614346
  10. [10]Kim JB O’Hare MJ Stein R Models of breast cancer: is merging human and animal models the future? Br. Cancer Res 2004 6 1 22 30 PMC314443 14680482
  11. [11]Pampaloni F Reynaud EG Stelzer EH The third dimension bridges the gap between cell culture and live tissue Nat. Rev 2007 8 10 839 845 17684528
  12. [12]Loessner D Stok KS Lutolf MP Hutmacher DW Clements JA Rizzi SC Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells Biomaterials 2010 31 32 8494 8506 20709389
  13. [13]Gurski LA Jha AK Zhang C Jia X Farach-Carson MC Hyaluronic acid-based hydrogels as 3D matrices for in vitro evaluation of chemotherapeutic drugs using poorly adherent prostate cancer cells Biomaterials 2009 30 30 6076 6085 19695694 PMC2782556
  14. [14]Horning JL Sahoo SK Vijayaraghavalu S Dimitrijevic S Vasir JK Jain TK Panda AK Labhasetwar V 3-D tumor model for in vitro evaluation of anticancer drugs Mol. Pharmaceutics 2008 5 5 849 862 18680382
  15. [15]Ng CP Pun SH A perfusable 3D cell-matrix tissue culture chamber for in situ evaluation of nanoparticle vehicle penetration and transport Biotechnol. Bioeng 2008 99 6 1490 1501 17969174 PMC2796126
  16. [16]Monazzam A Razifar P Simonsson M Qvarnstrom F Josephsson R Blomqvist C Langstrom B Bergstrom M Multicellular tumour spheroid as a model for evaluation of [18F]FDG as biomarker for breast cancer treatment monitoring Cancer Cell Int 2006 6 6 16556298 PMC1459213
  17. [17]Ong SM Zhao Z Arooz T Zhao D Zhang S Du T Wasser M van Noort D Yu H Engineering a scaffold-free 3D tumor model for in vitro drug penetration studies Biomaterials 2010 31 6 1180 1190 19889455
  18. [19]Friedrich J Seidel C Ebner R Kunz-Schughart LA Spheroid-based drug screen: considerations and practical approach Nat. Protocols 2009 4 3 309 324 19214182
  19. [20]Acharya G Shin CS McDermott M Mishra H Park H Kwon IC Park K The hydrogel template method for fabrication of homogeneous nano/microparticles J. Controlled Release 2010 141 3 314 319 19822178
  20. [21]Acharya G McDermott M Shin SJ Park H Park K Hurst SJ Hydrogel Templates for the Fabrication of Homogeneous Polymer Microparticles Biomedical Nanotechnology: Methods and Protocols 2011 New York Humana Press 726 179 185 21424450
  21. [23]Jayakrishnan A Jameela SR Glutaraldehyde as a fixative in bioprostheses and drug delivery matrices Biomaterials 1996 17 5 471 484 8991478
  22. [24]Yuan F Dellian M Fukumura D Leunig M Berk DA Torchilin VP Jain RK Vascular Permeability in a Human Tumor Xenograft: Molecular Size Dependence and Cutoff Size Cancer Res 1995 55 17 3752 3756 7641188
  23. [25]Lee SY Kim S Tyler JY Park K Cheng JX Blood-stable, tumor-adaptable disulfide bonded mPEG-(Cys)(4)-PDLLA micelles for chemotherapy Biomaterials 2013 34 2 552 561 23079665 PMC3489991
  24. [26]Shanskij YD Ershov YA Pechennikov VM A Method for Evaluation of Therapeutic Dose of Doxorubicin Hydrochloride Using Breast Tumor Cell Culture MCF-7 Bull. Exp. Biol. Med 2010 148 3 464 467 20396713
  25. [27]Lee GY Kenny PA Lee EH Bissell MJ Three-dimensional culture models of normal and malignant breast epithelial cells Nat. Methods 2007 4 4 359 365 17396127 PMC2933182
  26. [28]Plachot C Chaboub LS Adissu HA Wang L Urazaev A Sturgis J Asem EK Lelievre SA Factors necessary to produce basoapical polarity in human glandular epithelium formed in conventional and high-throughput three-dimensional culture: example of the breast epithelium BMC Biol 2009 7 77 19917093 PMC2784453
  27. [29]Cariati M Naderi A Brown JP Smalley MJ Pinder SE Caldas C Purushotham AD Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like subpopulation within the MCF7 breast cancer cell line Int. J. Cancer 2008 122 2 298 304 17935134
  28. [30]Chandramouly G Abad PC Knowles DW Lelievre SA The control of tissue architecture over nuclear organization is crucial for epithelial cell fate J. Cell Sci 2007 120 Pt 9 1596 1606 17405811
  29. [31]Cowin P Rowlands TM Hatsell SJ Cadherins and catenins in breast cancer Curr. Opin. Cell Biol 2005 17 5 499 508 16107313
  30. [32]Benton G Crooke E George J Laminin-1 induces E-cadherin expression in 3-dimensional cultured breast cancer cells by inhibiting DNA methyltransferase 1 and reversing promoter methylation status FASEB J 2009 23 11 3884 3895 19635753
  31. [33]Santini MT Rainaldi G Three-Dimensional Spheroid Model in Tumor Biology Pathobiology 1999 67 3 148 157 10394136
  32. [34]Lin RZ Chang HY Recent advances in three-dimensional multicellular spheroid culture for biomedical research Biotechnol. J 2008 3 9–10 1172 1184 18566957
  33. [35]Bigi A Cojazzi G Panzavolta S Rubini K Roveri N Mechanical and thermal properties of gelatin films at different degrees of glutaraldehyde crosslinking Biomaterials 2001 22 8 763 768 11246944
  34. [36]Bonvin C Overney J Shieh AC Dixon JB Swartz MA A multichamber fluidic device for 3D cultures under interstitial flow with live imaging: development, characterization, and applications Biotechnol. Bioeng 2010 105 5 982 991 19953672
  35. [37]Kwak B Park K Han B Tumor-on-Chip: Simulation of Complex Transport Around Tumor Proceedings of the ASME 2013 2nd Global Congress on Nanoengineering for Medicine and Biology 2013 Boston, MA NEMB2013-93314

Cited by

Sorted by citations

Authors
Shin, C. S., Kwak, B., Han, B., & Park, K.
Affiliations
Purdue University West Lafayette (US)
Corresponding author
Park, Kinam
ORCID
Venue
Molecular Pharmaceutics
Publisher
American Chemical Society (ACS)
Published
2013-03-06
Volume
10
Issue
6
Pages
2167-2175
ISSN
  • 1543-8384 (ISSN-L)
  • 1543-8392
DOI
10.1021/mp300595a
PMC
PMC3880422
OpenAlex
W2133379217
Cited by
135
References
0
Citations by year
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FWCI
7.91
Type
journal article
Language
en
Open access
Locations
  • Molecular Pharmaceutics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Purdue University
  • National Institutes of Health
  • National Cancer Institute (CA129287, R01CA129287)
  • National Institute of General Medical Sciences (GM095879, R01GM095879)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
tumor spheroids, 3D tumor models, hydrogel scaffolds, microwells, anticancer drug evaluation, drug delivery systems, microfluidic channels, tumor microenvironment, cell-matrix interactions, chemotherapy
MeSH terms
Antineoplastic Agents, Humans, Microscopy, Electron, Scanning, Neoplasms, Spheroids, Cellular, Hydrogel, Polyethylene Glycol Dimethacrylate, Cell Line, Tumor, Microfluidic Analytical Techniques

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