Cited by 84Cancer Cells and MetastasisLung Cancer Research StudiesLung Cancer Diagnosis and Treatment

Establishment of patient-derived tumor spheroids for non-small cell lung cancer

Open access
Zhang, Zengli, Wang, Huiqian, Ding, Qifeng, Xing, Yufei, Xu, Zhonghua, Lu, Chun, Luo, Dongdong, Xu, Longjiang +3 more·2018·PLOS ONE

Abstract

The prognosis of advanced non-small cell lung cancer (NSCLC) patients is poor. One of the reasons for this hampered progress has been a lack of in vitro models that would faithfully recapitulate the heterogeneity of tumors and response to treatment. In this study, surgically resected tumors were obtained from patients with stage I/II NSCLC during curative-intent surgery. Using a 3D patient-derived tumor spheroids culture system, our results demonstrate successful long-term expansion of primary NSCLC cells in vitro (> 120 days). Patient-derived tumor spheroid (PDS) cultures could be established with a success rate of 100% (3 out of 3 samples). Consistent with their growth in culture and their cancer type, many cells within the tumor spheroids were stained positive for Ki67 and thyroid transcription factor-1. The result of this study supports the establishment of an expandable 3D in vitro NSCLC model for drug screening, and enables the potential long term studies such as the establishment of drug resistant models.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0194016

Cites

Statistics

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Cisplatin is less effective in patient-derived organoids generated from non-small cell lung cancer tissues than in cell lines.

    “Cisplatin, for example, has been found to be less effective in patient-derived organoids (PDOs) generated from non-small cell lung cancer (NSCLC) tissues than from cell lines, highlighting the ability of patient-derived material to provide important information on potential resistance mechanisms.36”

    From Drug repurposing for cancer therapy (2024) · cites this paper as [36]

    Section 3.3 reports a higher cisplatin IC50 in patient-derived spheroids than values reported for most conventional 2D NSCLC cell lines, supporting the claim for that comparator. But the study’s direct comparison with H1299 cell-line spheroids found the difference in cisplatin cytotoxicity difficult to discern. The authors describe studying resistance mechanisms as a future step, not a finding of this study. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 14 · Cited by 84

Research works printed but not linked: 12

  1. [1]Tentler JJ, Tan AC, Weekes CD, Jimeno A, Leong S, Pitts TM, et al Patient-derived tumour xenografts as models for oncology drug development. Nature Reviews Clinical Oncology. 2012; 9 (6): 338– 350. doi: 10.1038/nrclinonc.2012.61 22508028 PMC3928688 · DOI · Paper page
  2. [2]Sia D, Moeini A, Labgaa I, Villanueva A. The future of patient-derived tumor xenografts in cancer treatment. Pharmacogenomics. 2015; 16 (14): 1671– 1683. doi: 10.2217/pgs.15.102 26402657 · DOI
  3. [5]Huang L, Holtzinger A, Jagan I, Begora M, Lohse I, Ngai N, et al Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell and patient-derived tumor organoids. Nature medicine. 2015; 21 (11): 1364– 1371. doi: 10.1038/nm.3973 26501191 PMC4753163 · DOI
  4. [6]Sato T, Vries RG, Snippert HJ, Van dWM, Barker N, Stange DE, et al Single Lgr5 stem cells build crypt–-villus structures in vitro without a mesenchymal niche. Nature. 2009; 459 (7244): 262– 265. doi: 10.1038/nature07935 19329995 · DOI · Paper page
  5. [7]Chen YW, Huang SX, Alrt DC, Ho SH, Islam MN, Volpi S, et al A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat Cell Biology. 2017; 19 (5): 542– 59. doi: 10.1038/ncb3510 28436965 PMC5777163 · DOI
  6. [8]Sato T, Clevers H. SnapShot: Growing Organoids from Stem Cells. Cell. 2015; 161(7): 1700 doi: 10.1016/j.cell.2015.06.028 26091044 · DOI · Paper page
  7. [9]Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, et al International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary. Proc Am Thorac Soc. 2011; 8 (5): 381– 385. doi: 10.1513/pats.201107-042ST 21926387 · DOI
  8. [10]Anagnostou VK, Syrigos KN, Bepler G, Homer RJ, Rimm DL. Thyroid transcription factor 1 is an independent prognostic factor for patients with stage I lung adenocarcinoma. J Clin Oncol. 2009; 27 (2): 271– 278. doi: 10.1200/JCO.2008.17.0043 19064983 · DOI
  9. [11]Barr MP, Gray SG, Hoffmann AC, Hilger RA, Thomale J, O'Flaherty JD, et al Generation and Characterisation of Cisplatin-Resistant Non-Small Cell Lung Cancer Cell Lines Displaying a Stem-Like Signature. PLOS ONE. 2013; 8 (1): e54193 doi: 10.1371/journal.pone.0054193 23349823 PMC3547914 · DOI · Paper page
  10. [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– 8496. doi: 10.1016/j.biomaterials.2010.07.064 20709389 · DOI · Paper page
  11. [13]Onion D, Argent RH, Reece-Smith AM, Craze ML, Pineda RG, Clarke PA, et al 3-Dimensional patient-derived lung cancer assays reveal resistance to standards-of-care promoted by stromal cells but sensitivity to histone deacetylase inhibitors. Molecular cancer therapeutics. 2016; 15(4): 753– 763. doi: 10.1158/1535-7163.MCT-15-0598 26873730 · DOI
  12. [14]Sandercock AM, Rust S, Guillard S, Sachsenmeier KF, Holoweckyj N, Hay C, et al Identification of anti-tumour biologics using primary tumour models, 3-D phenotypic screening and image-based multi-parametric profiling. Molecular cancer. 2015; 14(1): 147. 26227951 PMC4521473

Authors
Zhang, Z., Wang, H., Ding, Q., Xing, Y., Xu, Z., Lu, C., Luo, D., Xu, L., Xia, W., Zhou, C., & Shi, M.
Affiliations
  • Second Affiliated Hospital of Soochow University (CN)
  • Tongji University (CN)
Corresponding author
  • Zhou, Caicun
  • Shi, Minhua
Venue
PLOS ONE
Published
2018-03-15
Volume
13
Issue
3
Pages
e0194016
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2790797622
Cited by
84
References
14
Citations by year
2026: 3 · 2025: 8 · 2024: 17 · 2023: 12 · 2022: 15 · 2021: 13 · 2020: 8 · 2019: 7 · 2018: 1
FWCI
2.73
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Preponderant Clinic Discipline Group Project Funding (XKQ2015OO5)
  • the Suzhou Municipal Key Medical Disciplines (Respiratory Medicine) grant (SZXK201506)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords
non-small cell lung cancer, 3D tumor culture, in vitro tumor model, Ki-67, TTF-1, drug screening, early-stage lung cancer
MeSH terms
Thyroid Nuclear Factor 1, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Spheroids, Cellular, Cell Culture Techniques, Ki-67 Antigen, Cell Line, Tumor

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