The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Time series assessment of the effects of hypoxic stress on glioma tumorsphere development within engineered microscale niches
Abstract
A rapidly outgrowing tumor mass is liable to suffer from a shortage of oxygen and nutrients due to the diffusion limit. These features evidently prevail in glioblastoma, resulting in extensive hypoxic regions throughout the tumor mass. While there may be a strong link between hypoxic regions and glioblastoma malignancy, the effects of hypoxia stress on each tumorigenic step and their interrelation during the progression remain unexplored due to the limited information from current assay platforms. Here, we suggest a tumor microenvironment array platform (TMAP) to describe a time series assessment of glioblastoma tumorsphere (TS) within a microscale niche. TMAP enables to observe the overall tumorigenic process of glioblastoma TSs over the cultivation time, simultaneously quantifying the features with the biophysical parameters. Through the time series assessment, we observed the induction of hypoxic stress within the mature TSs, which rendered intratumoral phenotypic changes to become more malignant and modulated their microenvironmental niches to enhance angiogenic proliferation, immune recruitment, and even drug response. Based on the finding that the tumorigenic parameters were highly correlated only in mature TSs, we conclude that the effects of hypoxic stress systematically affect the process that drives a glioblastoma to higher malignancy.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“recently published literature discusses the role of the size of a tumor (and the associated hypoxia levels) on its aggressiveness [81,82,83,84,85] and on the efficacy of drug delivery to it [84,86,87].”
From The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors (2019) · cites this paper as [82]
Citations
Cites
Spheroid culture as a tool for creating 3D complex tissues
Fennema, E., Rivron, N., Rouwkema, J., van Blitterswijk, C., & de Boer, J. (2013) · Trends in Biotechnology · doi:10.1016/j.tibtech.2012.12.003 · Cited by 1,054
A versatile 3D tissue matrix scaffold system for tumor modeling and drug screening
Rijal, G., & Li, W. (2017) · Science Advances · doi:10.1126/sciadv.1700764 · Cited by 154
Tumor cells and their crosstalk with endothelial cells in 3D spheroids
Shoval, H., Karsch-Bluman, A., Brill-Karniely, Y., Stern, T., Zamir, G., Hubert, A., & Benny, O. (2017) · Scientific Reports · doi:10.1038/s41598-017-10699-y · Cited by 138
Research works printed but not linked: 28
- Joyce, 2009, Microenvironmental regulation of metastasis, Nat. Rev. Canc., 9, 239, 10.1038/nrc2618 · DOI · Paper page
- Egeblad, 2010, Tumors as organs: complex tissues that interface with the entire organism, Dev. Cell, 18, 884, 10.1016/j.devcel.2010.05.012 · DOI
- Gilbertson, 2007, Making a tumour's bed: glioblastoma stem cells and the vascular niche, Nat. Rev. Canc., 7, 733, 10.1038/nrc2246 · DOI
- Tafani, 2011, Pro-inflammatory gene expression in solid glioblastoma microenvironment and in hypoxic stem cells from human glioblastoma, J. Neuroinflammation, 8, 32, 10.1186/1742-2094-8-32 · DOI
- Cheng, 2013, Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth, Cell, 153, 139, 10.1016/j.cell.2013.02.021 · DOI · Paper page
- da Fonseca, 2013, Microglia and macrophages in malignant gliomas: recent discoveries and implications for promising therapies, Clin. Dev. Immunol., 2013
- Marusyk, 2012, Intra-tumour heterogeneity: a looking glass for cancer?, Nat. Rev. Canc., 12, 323, 10.1038/nrc3261 · DOI
- Yin, 2016, Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis, Nat. Commun., 7, 11311, 10.1038/ncomms11311 · DOI
- Gilkes, 2014, Hypoxia and the extracellular matrix: drivers of tumour metastasis, Nat. Rev. Canc., 14, 430, 10.1038/nrc3726 · DOI · Paper page
- Weiswald, 2015, Spherical cancer models in tumor biology, Neoplasia, 17, 1, 10.1016/j.neo.2014.12.004 · DOI
- Pistollato, 2010, Intratumoral hypoxic gradient drives stem cells distribution and MGMT expression in glioblastoma, Stem Cell., 28, 851, 10.1002/stem.415 · DOI
- Li, 2009, Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells, Cancer Cell, 15, 501, 10.1016/j.ccr.2009.03.018 · DOI · Paper page
- Joseph, 2015, Hypoxia enhances migration and invasion in glioblastoma by promoting a mesenchymal shift mediated by the HIF1alpha-ZEB1 axis, Cancer Lett., 359, 107, 10.1016/j.canlet.2015.01.010 · DOI
- Kitange, 2009, Induction of MGMT expression is associated with temozolomide resistance in glioblastoma xenografts, Neuro Oncol., 11, 281, 10.1215/15228517-2008-090 · DOI
- Jain, 2006, Lessons from phase III clinical trials on anti-VEGF therapy for cancer, Nat. Clin. Pract. Oncol., 3, 24, 10.1038/ncponc0403 · DOI
- Omuro, 2007, Lessons learned in the development of targeted therapy for malignant gliomas, Mol. Canc. Therapeut., 6, 1909, 10.1158/1535-7163.MCT-07-0047 · DOI
- Cha, 2016, Strategies of mesenchymal invasion of patient-derived brain tumors: microenvironmental adaptation, Sci. Rep., 6, 24912, 10.1038/srep24912 · DOI
- Cuddapah, 2014, A neurocentric perspective on glioma invasion, Nat. Rev. Neurosci., 15, 455, 10.1038/nrn3765 · DOI
- Zanoni, 2016, 3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained, Sci. Rep., 6, 19103, 10.1038/srep19103 · DOI · Paper page
- Desoize, 1998, Cell culture as spheroids: an approach to multicellular resistance, Anticancer Res., 18, 4147
- Desoize, 2000, Multicellular resistance: a paradigm for clinical resistance?, Crit. Rev. Oncol. Hematol., 36, 193, 10.1016/S1040-8428(00)00086-X · DOI
- Quail, 2013, Microenvironmental regulation of tumor progression and metastasis, Nat. Med., 19, 1423, 10.1038/nm.3394 · DOI · Paper page
- Zujur, 2017, Three-dimensional system enabling the maintenance and directed differentiation of pluripotent stem cells under defined conditions, Sci. Adv., 3, 10.1126/sciadv.1602875 · DOI
- Hood, 2002, Role of integrins in cell invasion and migration, Nat. Rev. Canc., 2, 91, 10.1038/nrc727 · DOI
- Facciabene, 2011, Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells, Nature, 475, 226, 10.1038/nature10169 · DOI · Paper page
- Li, 2013, Hypoxia enhances stemness of cancer stem cells in glioblastoma: an in vitro study, Int. J. Med. Sci., 10, 399, 10.7150/ijms.5407 · DOI
- Patel, 2014, Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma, Science, 344, 1396, 10.1126/science.1254257 · DOI · Paper page
- Friedrich, 2009, Spheroid-based drug screen: considerations and practical approach, Nat. Protoc., 4, 309, 10.1038/nprot.2008.226 · DOI · Paper page
Cited by
Sorted by citations
Trujillo-de Santiago, G., Flores-Garza, B. G., Tavares-Negrete, J. A., Lara-Mayorga, I. M., González-Gamboa, I., Zhang, Y. S., Rojas-Martínez, A., Ortiz-López, R., & Álvarez, M. M. (2019) · Materials · doi:10.3390/ma12182945 · Cited by 184
Metadata
- Authors
- Cha, J., & Kim, P.
- Affiliations
- Korea Advanced Institute of Science and Technology (KR)
- Corresponding author
- Kim, Pilnam
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 194
- Pages
- 171-182
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2904133339
- Cited by
- 8
- References
- 3
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health and Welfare (HI14C1324)
- Korea Health Industry Development Institute
- Ministry of Education (NRF-2018R1A6A3A01012494)
- National Research Foundation of Korea
- Ministry of Science, ICT and Future Planning (KAISTHEALTHCARE42)
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- glioblastoma, hypoxia, tumor spheres, tumor microenvironment, tumor malignancy, angiogenesis, drug response, biophysical parameters
- MeSH terms
- Tumor Hypoxia, Brain Neoplasms, Glioblastoma, Humans, Time Factors, Oxidative Stress, Cell Culture Techniques, Cell Line, Tumor, Tumor Microenvironment, Human Umbilical Vein Endothelial Cells, Carcinogenesis
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
