The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Chitosan–alginate 3D scaffolds as a mimic of the glioma tumor microenvironment
Open accessAbstract
Despite recent advances in the understanding of its cell biology, glioma remains highly lethal. Development of effective therapies requires a cost-effective in vitro tumor model that more accurately resembles the in vivo tumor microenvironment as standard two-dimensional (2D) tissue culture conditions do so poorly. Here we report on the use of a three-dimensional (3D) chitosan-alginate (CA) scaffold to serve as an extracellular matrix that promotes the conversion of cultured cancer cells to a more malignant in vivo-like phenotype. Human U-87 MG and U-118 MG glioma cells and rat C6 glioma cells were chosen for the study. In vitro tumor cell proliferation and secretion of factors that promote tumor malignancy, including VEGF, MMP-2, fibronectin, and laminin, were assessed. The scaffolds pre-cultured with U-87 MG and C6 cells were then implanted into nude mice to evaluate tumor growth and blood vessel recruitment compared to the standard 2D cell culture and 3D Matrigel matrix xenograft controls. Our results indicate that while the behavior of C6 cells showed minimal differences due to their highly malignant and invasive nature, U-87 MG and U-118 MG cells exhibited notably higher malignancy when cultured in CA scaffolds. CA scaffolds provide a 3D microenvironment for glioma cells that is more representative of the in vivo tumor, thus can serve as a more effective platform for development and study of anticancer therapeutics. This unique CA scaffold platform may offer a valuable alternative strategy to the time-consuming and costly animal studies for a wide variety of experimental designs.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Lutolf, M. P., & Hubbell, J. A. (2005) · Nature Biotechnology · doi:10.1038/nbt1055 · Cited by 4,551
Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene
Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O’Shea, K. S., Powell-Braxton, L., Hillan, K. J., & Moore, M. W. (1996) · Nature · doi:10.1038/380439a0 · Cited by 3,661
Plate, K. H., Breier, G., Weich, H. A., & Risau, W. (1992) · Nature · doi:10.1038/359845a0 · Cited by 2,262
Weaver, V. M., Petersen, O. W., Wang, F., Larabell, C. A., Briand, P., Damsky, C., & Bissell, M. J. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.1.231 · Cited by 1,483
PETERSEN, O. W., Rønnov‐Jessen, L., Howlett, A. R., & Bissell, M. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.19.9064 · Cited by 1,096
Chitosan–alginate hybrid scaffolds for bone tissue engineering
Li, Z., Ramay, H. R., Hauch, K. D., Xiao, D., & Zhang, M. (2004) · Biomaterials · doi:10.1016/j.biomaterials.2004.09.062 · Cited by 1,068
Self-citationPersistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line
Kondo, T., Setoguchi, T., & Taga, T. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307618100 · Cited by 993
Mechanics, malignancy, and metastasis: The force journey of a tumor cell
Kumar, S., & Weaver, V. M. (2009) · Cancer and Metastasis Reviews · doi:10.1007/s10555-008-9173-4 · Cited by 966
Engineering tumors with 3D scaffolds
Fischbach, C., Chen, R., Matsumoto, T., Schmelzle, T., Brugge, J. S., Polverini, P. J., & Mooney, D. J. (2007) · Nature Methods · doi:10.1038/nmeth1085 · Cited by 834
Yamaguchi, H., Wyckoff, J. B., & Condeelis, J. S. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.08.002 · Cited by 769
Wang, F., Weaver, V. M., Petersen, O. W., Larabell, C. A., Dedhar, S., Briand, P., Lupu, R., & Bissell, M. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14821 · Cited by 653
Mirimanoff, R. O., Gorlia, T., Mason, W. P., van den Bent, M. J., Kortmann, R., Fisher, B., Reni, M., Brandes, A. A., Curschmann, J., Villà, S., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.5963 · Cited by 510
Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly
O’Brien, L. E., Jou, T., Pollack, A. L., Zhang, Q., Hansen, S. H., Yurchenco, P. D., & Mostov, K. E. (2001) · Nature Cell Biology · doi:10.1038/ncb0901-831 · Cited by 485
Autocrine Factors That Sustain Glioma Invasion and Paracrine Biology in the Brain Microenvironment
Hoelzinger, D. B., Demuth, T., & Berens, M. E. (2007) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djm187 · Cited by 370
Biocompatibility of alginate–poly-l-lysine microcapsules for cell therapy
Orive, G., Tam, S. K., Pedraz, J. L., & Hallé, J. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.02.048 · Cited by 338
LIFE ISN'T FLAT: TAKING CANCER BIOLOGY TO THE NEXT DIMENSION
Smalley, K. S. M., Lioni, M., & Herlyn, M. (2006) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1290/0604027.1 · Cited by 301
Chitosan–alginate as scaffolding material for cartilage tissue engineering
Li, Z., & Zhang, M. (2005) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30449 · Cited by 237
Self-citationMost C6 Cells Are Cancer Stem Cells: Evidence from Clonal and Population Analyses
Zheng, X., Shen, G., Yang, X., & Liu, W. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3912 · Cited by 217
From Genes to Gene Medicines: Recent Advances in Nonviral Gene Delivery
Rolland, A. P. (1998) · Critical Reviews in Therapeutic Drug Carrier Systems · doi:10.1615/critrevtherdrugcarriersyst.v15.i2.20 · Cited by 208
Conditional ROCK Activation In vivo Induces Tumor Cell Dissemination and Angiogenesis
Croft, D. R., Sahai, E. A., Mavria, G., Li, S., Tsai, J. H., Lee, W. M. F., Marshall, C. J., & Olson, M. F. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-2052 · Cited by 165
Feeder-free self-renewal of human embryonic stem cells in 3D porous natural polymer scaffolds
Li, Z., Leung, M., Hopper, R., Ellenbogen, R., & Zhang, M. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2009.09.070 · Cited by 160
Self-citationIs Anticancer Drug Development Heading in the Right Direction?
Hambley, T. W. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3786 · Cited by 153
Affoué, M., Laurent, L., Ploton, D., Poupon, M., Jc, J., & Bobichon, H. (2002) · Clinical & Experimental Metastasis · doi:10.1023/a:1014594825502 · Cited by 135
Antitumor efficacy of a novel polymer-peptide-drug conjugate in human tumor xenograft models
Chau, Y., Padera, R. F., Dang, N. M., & Langer, R. (2005) · International Journal of Cancer · doi:10.1002/ijc.21495 · Cited by 126
Fabrication of well-defined PLGA scaffolds using novel microembossing and carbon dioxide bonding
Yang, Y. S., Basu, S., Tomasko, D. L., Lee, L. J., & Yang, S. (2004) · Biomaterials · doi:10.1016/j.biomaterials.2004.07.046 · Cited by 77
Shen, G., Shen, F., Shi, Z., Liu, W., Hu, W., Zheng, X., Wen, L., & Yang, X. (2008) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-008-9115-z · Cited by 65
Jouanneau, E. (2008) · Neurosurgery · doi:10.1227/01.neu.0000311060.65002.4e · Cited by 60
Human and Rat Glioma Growth, Invasion, and Vascularization in a Novel Chick Embryo Brain Tumor Model
Cretu, A., Fotos, J. S., Little, B. W., & Galileo, D. S. (2005) · Clinical & Experimental Metastasis · doi:10.1007/s10585-005-7889-x · Cited by 42
Targeted Therapies for Malignant Glioma: Progress and Potential
Mercer, R. W., Tyler, M. A., Ulasov, I. V., & Lesniak, M. S. (2009) · BioDrugs · doi:10.2165/00063030-200923010-00003 · Cited by 39
Flagged first, then by citations
Research works printed but not linked: 1
- Hirano, 1988, Biocompatibility of chitosan by oral and intravenous administration, Crit Rev Ther Drug Carrier Syst, 15, 143
Cited by
Sorted by citations
Luo, Y., & Wang, Q. (2013) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2013.12.017 · Cited by 837
In Vitro Tumor Models: Advantages, Disadvantages, Variables, and Selecting the Right Platform
Katt, M. E., Placone, A. L., Wong, A. D., Xu, Z. S., & Searson, P. C. (2016) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2016.00012 · Cited by 754
Yi, H.-G., Jeong, Y. H., Kim, Y., Choi, Y.-J., Moon, H. E., Park, S. H., Kang, K. S., Bae, M., Jang, J., Youn, H., et al. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0363-x · Cited by 634
Aptamer-functionalized PEG–PLGA nanoparticles for enhanced anti-glioma drug delivery
Guo, J., Gao, X., Su, L., Xia, H., Gu, G., Pang, Z., Jiang, X., Yao, L., Chen, J., & Chen, H. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.07.004 · Cited by 567
Three-dimensional printing of Hela cells for cervical tumor model in vitro
Zhao, Y., Yao, R., Ouyang, L., Ding, H., Zhang, T., Zhang, K., Cheng, S., & Sun, W. (2014) · Biofabrication · doi:10.1088/1758-5082/6/3/035001 · Cited by 549
Metadata
- Authors
- Kievit, F. M., Florczyk, S. J., Leung, M. C., Veiseh, O., Park, J. O., Disis, M. L., & Zhang, M.
- Affiliations
- University of Washington (US)
- Corresponding author
- Zhang, Miqin
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 31
- Issue
- 22
- Pages
- 5903-5910
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC2883048
- OpenAlex
- W2078576156
- Cited by
- 209
- References
- 29
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 3 · 2023: 19 · 2022: 14 · 2021: 14 · 2020: 21 · 2019: 12 · 2018: 14 · 2017: 10 · 2016: 17 · 2015: 17 · 2014: 14 · 2013: 22 · 2012: 7
- FWCI
- 6.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- National Institutes of Health
- National Cancer Institute (U01CA141539, R01CA134213, T32CA138312, R01CA119408)
- National Institute of Biomedical Imaging and Bioengineering (R01EB006043)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Keywords
- glioma, 3D tumor models, tumor microenvironment, extracellular matrix, U87 cells, C6 glioma cells, vascular endothelial growth factor, MMP-2, fibronectin, laminin, tumor angiogenesis, tumor growth, xenografts, anticancer drug screening
- MeSH terms
- Alginates, Animals, Cell Transformation, Neoplastic, Glioma, Hexuronic Acids, Humans, Male, Mice, Nude, Neovascularization, Pathologic, Glucuronic Acid, Cell Line, Tumor, Chitosan, Mice, Rats, Tissue Scaffolds
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
