Molecular description of a 3D in vitro model for the study of epithelial ovarian cancer (EOC)
Abstract
Epithelial ovarian cancer (EOC) cell lines are useful tools for the molecular and biological characterization of ovarian cancer. The use of an in vitro multidimensional (3‐D) culture model recapitulates some of the growth conditions encountered by tumor cells in vivo. Here we describe a molecular comparison of spheroid based 3D EOC models versus monolayer cultures and xenografts using cell lines from malignant ovarian tumors (TOV‐21G and TOV‐112D) and ascites (OV‐90) previously established and characterized in our laboratory. Gene expression analyses of the three models were performed using the Affymetrix HG‐U133A high density DNA array. Cluster analysis identified a set of genes that stratified expression profiles from the EOC cell lines grown as spheroids and xenografts from that of monolayer cultures. The gene expression analysis results were validated by Q‐PCR analyses on an independent set of RNAs. Differential expression observed for the S100A6 gene between the monolayer, spheroid cultures and xenografts was confirmed at the protein level by immunohistochemistry. The analysis was extended to various ovarian tumor tissues using an EOC tissue array. This result represents an example of a gene that, if studied in vitro, is more representative of the in vivo disease in a 3D model rather than the monolayer culture. Identification of genes in spheroid models that mimic the in vivo tumor gene expression patterns may allow a better understanding of the community effect observed in human disease that is determined by direct or indirect interactions of cells with their environment or other surrounding cells. © 2007 Wiley‐Liss, Inc.
Integrity signals
Registry
Cites
Statistics
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?
Cell responses in 3D cultures are more similar to in vivo behavior compared to 2D culture.
“It has been demonstrated that cell responses in 3D cultures are more similar to in vivo behavior compared to 2D culture. 11-13”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [12]
Cellular responses to drug treatments in 3D cultures are more similar to what occurs in vivo compared to 2D culture.
“Cellular responses to drug treatments in 3D cultures have been shown to be more similar to what occurs in vivo compared to 2D culture. 11-13”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [12]
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610 · see citing works
Exploration, normalization, and summaries of high density oligonucleotide array probe level data
Irizarry, R. A. (2003) · Biostatistics · doi:10.1093/biostatistics/4.2.249 · Cited by 10,603 · see citing works
Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis
Hanahan, D., & Folkman, J. (1996) · Cell · doi:10.1016/s0092-8674(00)80108-7 · Cited by 6,885 · see citing works
Cell and environment interactions in tumor microregions: the multicell spheroid model.
Sutherland, R. M. (1988) · Science · doi:10.1126/science.2451290 · Cited by 1,803 · see citing works
Ovarian Surface Epithelium: Biology, Endocrinology, and Pathology
Auersperg, N., Wong, A. S. T., Choi, K., Kang, S. K., & Leung, P. C. K. (2001) · Endocrine Reviews · doi:10.1210/edrv.22.2.0422 · Cited by 1,040 · see citing works
In vitro differentiation of embryonic stem cells
Keller, G. M. (1995) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(95)80071-9 · Cited by 953 · see citing works
Kelm, J. M., Timmins, N. E., Brown, C. J., Fussenegger, M., & Nielsen, L. K. (2003) · Biotechnology and Bioengineering · doi:10.1002/bit.10655 · Cited by 934 · see citing works
Marenholz, I., Heizmann, C. W., & Fritz, G. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.07.096 · Cited by 842 · see citing works
(2002) · PubMed · Cited by 840 · see citing works
The use of 3-d cultures for high-throughput screening: the multicellular spheroid model.
Kunz-Schughart, L. A., Freyer, J. P., Hofstaedter, F., & Ebner, R. (2004) · SLAS DISCOVERY · doi:10.1177/1087057104265040 · Cited by 797 · see citing works
Ovarian Surface Epithelium: Biology, Endocrinology, and Pathology
Auersperg, N. (2001) · Endocrine Reviews · doi:10.1210/er.22.2.255 · Cited by 439 · see citing works
Schwartz, D. R., Kardia, S. L. R., Shedden, K., et al. (2002) · PubMed · Cited by 429 · see citing works
Multicellular resistance: a paradigm for clinical resistance?
Desoize, B. (2000) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(00)00086-x · Cited by 400 · see citing works
Control of actin assembly and disassembly at filament ends
Cooper, J. A., & Schafer, D. A. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)00062-9 · Cited by 337 · see citing works
Multicellular spheroids: a three‐dimensionalin vitroculture system to study tumour biology
Kunz‐Schughart, L. A., Kreutz, M. P., & Knuechel, R. (1998) · International Journal of Experimental Pathology · doi:10.1046/j.1365-2613.1998.00051.x · Cited by 326 · see citing works
Cytoskeletal changes in cell transformation and tumorigenesis
Pawlak, G., & Helfman, D. M. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00154-4 · Cited by 322 · see citing works
Three-dimensional in vitro tissue culture models of breast cancer — a review
Kim, J. B., Stein, R. C., & O'Hare, M. J. (2004) · Breast Cancer Research and Treatment · doi:10.1023/b:brea.0000025418.88785.2b · Cited by 315 · see citing works
Open Source Software for the Analysis of Microarray Data
Dudoit, S., Gentleman, R. C., & Quackenbush, J. F. (2003) · BioTechniques · doi:10.2144/mar03dudoit · Cited by 281 · see citing works
Spheroid Preparation from Hanging Drops: Characterization of a Model of Brain Tumor Invasion
Duca, D. D., Werbowetski‐Ogilvie, T. E., & Maestro, R. F. D. (2004) · Journal of Neuro-Oncology · doi:10.1023/b:neon.0000024220.07063.70 · Cited by 270 · see citing works
Burleson, K. M., Casey, R. C., Skubitz, K. M., Pambuccian, S. E., Oegema, T. R., & Skubitz, A. P. N. (2004) · Gynecologic Oncology · doi:10.1016/j.ygyno.2003.12.034 · Cited by 269 · see citing works
Cross, S. S., Hamdy, F. C., Deloulme, J., & Rehman, I. (2005) · Histopathology · doi:10.1111/j.1365-2559.2005.02097.x · Cited by 259 · see citing works
Differential Gene Expression in Ovarian Carcinoma
Hibbs, K., Skubitz, K. M., Pambuccian, S. E., Casey, R. C., Burleson, K. M., Oegema, T. R., Thiele, J. J., Grindle, S. M., Bliss, R., & Skubitz, A. P. N. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63306-8 · Cited by 256 · see citing works
Regulation of tumor angiogenesis by thrombospondin-1
Ren, B., Yee, K. O., Lawler, J., & Khosravi‐Far, R. (2005) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2005.11.002 · Cited by 225 · see citing works
Multicellular tumor spheroids: intermediates between monolayer culture and in vivo tumor
Kunz‐Schughart, L. A. (1999) · Cell Biology International · doi:10.1006/cbir.1999.0384 · Cited by 217 · see citing works
Epithelial Cell Plasticity in Development and Tumor Progression
Thiery, J., & Chopin, D. (2004) · Cancer Metastasis Review · doi:10.1023/a:1006256219004 · Cited by 209 · see citing works
Schmidt-Hansen, B., Örnås, D., Grigorian, M., Klingelhöfer, J., Tulchinsky, E. M., Lukanidin, E. M., & Ambartsumian, N. S. (2004) · Oncogene · doi:10.1038/sj.onc.1207720 · Cited by 195 · see citing works
Santini, M. T. (2000) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(00)00078-0 · Cited by 189 · see citing works
Hanging-drop multicellular spheroids as a model of tumour angiogenesis
Timmins, N., Dietmair, S., & Nielsen, L. K. (2004) · Angiogenesis · doi:10.1007/s10456-004-8911-7 · Cited by 177 · see citing works
Wartenberg, M., Dönmez, F., Ling, F. C., Acker, H., Hescheler, J., & Sauer, H. (2001) · The FASEB Journal · doi:10.1096/fj.00-0350com · Cited by 173 · see citing works
Ohuchida, K., Mizumoto, K., Ishikawa, N., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0714 · Cited by 169 · see citing works
Frankel, A., Buckman, R. A., & Kerbel, R. S. (1997) · PubMed · Cited by 168 · see citing works
The Cellular Basis of Tumor Progression
Heppner, G. H., & Miller, F. R. (1997) · International review of cytology · doi:10.1016/s0074-7696(08)62230-5 · Cited by 161 · see citing works
Expression analysis of S100 proteins and RAGE in human tumors using tissue microarrays
Hsieh, H.-L., Schäfer, B. W., Sasaki, N., & Heizmann, C. W. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01190-2 · Cited by 151 · see citing works
Vimalachandran, D., Greenhalf, W., Thompson, C. C., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4311 · Cited by 143 · see citing works
S100 proteins and their influence on pro-survival pathways in cancer
Emberley, E. D., Murphy, L. C., & Watson, P. H. (2004) · Biochemistry and Cell Biology · doi:10.1139/o04-052 · Cited by 139 · see citing works
Thrombospondin 1: a multifunctional protein implicated in the regulation of tumor growth
Sid, B., Sartelet, H., Bellon, G., et al. (2004) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2003.09.009 · Cited by 107 · see citing works
Hypoxic Cells in an in Vitro Tumour Model
Sutherland, R. M., & Durand, R. E. (1973) · International Journal of Radiation Biology and Related Studies in Physics Chemistry and Medicine · doi:10.1080/09553007314550261 · Cited by 93 · see citing works
Cell culture as spheroids: an approach to multicellular resistance.
Desoize, B., Gimonet, D., & Jardiller, J. C. (1999) · PubMed · Cited by 88 · see citing works
Early events in ovarian epithelial carcinogenesis: progress and problems in experimental approaches
Auersperg, N., Ota, T., & Mitchell, G. W. E. (2002) · International Journal of Gynecological Cancer · doi:10.1046/j.1525-1438.2002.01152.x · Cited by 88 · see citing works
Laser capture microdissection: beyond functional genomics to proteomics.
Simone, N. L., Paweletz, C. P., Charboneau, L., et al. (2000) · PubMed · doi:10.1007/bf03262091 · Cited by 84 · see citing works
Sheibani, N., Newman, P. J., & Frazier, W. A. (1997) · Molecular Biology of the Cell · doi:10.1091/mbc.8.7.1329 · Cited by 82 · see citing works
Komatsu, K., Andoh, A., Ishiguro, S., et al. (2000) · PubMed · Cited by 78 · see citing works
Microarray analysis of gene expression mirrors the biology of an ovarian cancer model
Tonin, P. N., Hudson, T. J., Rodier, F., et al. (2001) · Oncogene · doi:10.1038/sj.onc.1204804 · Cited by 77 · see citing works
Self-citationLaser Capture Microdissection: Beyond Functional Genomics to Proteomics
Simone, N. L., Paweletz, C. P., Charboneau, L., et al. (2000) · Molecular Diagnosis · doi:10.2165/00066982-200005040-00008 · Cited by 77 · see citing works
Mayer, B., Klement, G. L., Kaneko, M., Man, S., Jothy, S., Rak, J. W., & Kerbel, R. S. (2001) · Gastroenterology · doi:10.1053/gast.2001.27989 · Cited by 76 · see citing works
Wartenberg, M., Dönmez, F., Ling, F. C., et al. (2001) · The FASEB Journal · doi:10.1096/fsb2fj000350com · Cited by 69 · see citing works
Gilead, A., Meir, G., & Neeman, M. (2003) · International Journal of Cancer · doi:10.1002/ijc.11583 · Cited by 62 · see citing works
Francia, G., Man, S., Teicher, B. A., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.15.6837-6849.2004 · Cited by 59 · see citing works
Early events in ovarian oncogenesis
Cvetković, D. (2003) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-1-68 · Cited by 54 · see citing works
Expression of S100A2 and S100A6 in thyroid carcinomas
Ito, Y., Yoshida, H., Tomoda, C., et al. (2005) · Histopathology · doi:10.1111/j.1365-2559.2005.02137.x · Cited by 53 · see citing works
Samou�lian, V., Maugard, C. M., Jolicoeur, M. E., et al. (2004) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-004-0843-9 · Cited by 49 · see citing works
Self-citationEffect of therapeutic macromolecules in spheroids.
Fracasso, G. (2000) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(00)00084-6 · Cited by 46 · see citing works
Wartenberg, M., Schallenberg, M., Hescheler, J., & Sauer, H. (2003) · International Journal of Cancer · doi:10.1002/ijc.10928 · Cited by 44 · see citing works
Sonoda, T., Kobayashi, H., Kaku, T., Hirakawa, T., & Nakano, H. (2003) · Cancer Letters · doi:10.1016/s0304-3835(03)00216-7 · Cited by 40 · see citing works
Spheroids: relation between tumour and endothelial cells
Oudar, O. (2000) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(00)00080-9 · Cited by 33 · see citing works
Signature of a silent killer: expression profiling in epithelial ovarian cancer
Page, C. L., Provencher, D. M., Maugard, C. M., et al. (2004) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.4.2.157 · Cited by 32 · see citing works
Self-citationPresneau, N., Mes‐Masson, A., Ge, B., et al. (2003) · Oncogene · doi:10.1038/sj.onc.1206219 · Cited by 31 · see citing works
Self-citationFilipek, A. (2005) · Chemotherapy · doi:10.1159/000090240 · Cited by 29 · see citing works
Robertson, D. M., Pruysers, E., Burger, H., et al. (2004) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2004.02.014 · Cited by 29 · see citing works
Baijal‐Gupta, M., Clarke, M. W., FINKELMAN, M. A., et al. (2000) · Journal of Endocrinology · doi:10.1677/joe.0.1650425 · Cited by 29 · see citing works
Rainaldi, G., Calcabrini, A., Arancia, G., & Santini, M. T. (1999) · PubMed · Cited by 26 · see citing works
Upstream stimulatory factor is involved in the regulation of the human calcyclin (S100A6) gene
Leśniak, W., Jezierska, A., & Kuźnicki, J. (2000) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(00)00259-1 · Cited by 24 · see citing works
Franko, A., Parliament, M. B., Allalunis‐Turner, M. J., et al. (1998) · British Journal of Cancer · doi:10.1038/bjc.1998.669 · Cited by 24 · see citing works
Arcand, S. L., Mes‐Masson, A., Provencher, D. M., Hudson, T. J., & Tonin, P. N. (2004) · Molecular Carcinogenesis · doi:10.1002/mc.20038 · Cited by 22 · see citing works
Self-citationTanaka, R., Saito, T., Ashihara, K., Nishimura, M., Mizumoto, H., & Kudo, R. (2003) · Gynecologic Oncology · doi:10.1016/s0090-8258(03)00335-4 · Cited by 21 · see citing works
Manderson, E. N., Mes‐Masson, A., Novak, J., et al. (2002) · Genome Research · doi:10.1101/gr.174202 · Cited by 21 · see citing works
Self-citationInhibins as Biomarkers for Reproductive Cancers
Robertson, D. M., & McNeilage, J. (2004) · Seminars in Reproductive Medicine · doi:10.1055/s-2004-831897 · Cited by 16 · see citing works
AGED GARLIC EXTRACT SUPPRESSES LIPID PEROXIDATION INDUCED BY β-AMYLOID IN PC12 CELLS
Griffin, B., Selassie, M., & Gwebu, E. T. (2000) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1290/1071-2690(2000)036 · Cited by 8 · see citing works
Manderson, E. N., Mes‐Masson, A., Provencher, D. M., et al. (2000) · Clinical Genetics · doi:10.1034/j.1399-0004.2000.570211.x · Cited by 7 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Edmondson, R., Broglie, J. J., Adcock, A. F., & Yang, L. (2014) · ASSAY and Drug Development Technologies · doi:10.1089/adt.2014.573 · Cited by 2,515 · see citing works
Spheroid-based drug screen: Considerations and practical approach
Friedrich, J., Seidel, C., Ebner, R., & Kunz-Schughart, L. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.226 · Cited by 1,742 · see citing works
Loessner, D., Stok, K. S., Lutolf, M. P., Hutmacher, D. W., Clements, J. A., & Rizzi, S. C. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.07.064 · Cited by 602 · see citing works
Hoarau-Véchot, J., Rafii, A., Touboul, C., & Pasquier, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010181 · Cited by 489 · see citing works
Matrigel: From discovery and ECM mimicry to assays and models for cancer research
Benton, G., Arnaoutova, I., George, J., Kleinman, H. K., & Koblinski, J. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.06.005 · Cited by 477 · see citing works
Multicellular spheroids in ovarian cancer metastases: Biology and pathology
Shield, K., Ackland, M. L., Ahmed, N., & Rice, G. E. (2009) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.11.032 · Cited by 412 · see citing works
Three-Dimensional In Vitro Co-Culture Model of Breast Tumor using Magnetic Levitation
Jaganathan, H., Gage, J., Leonard, F., Srinivasan, S., Souza, G. R., Dave, B., & Godin, B. (2014) · Scientific Reports · doi:10.1038/srep06468 · Cited by 231 · see citing works
Micro-dissected tumor tissues on chip: an ex vivo method for drug testing and personalized therapy
Astolfi, M., Péant, B., Lateef, M. A., Rousset, N., Kendall-Dupont, J., Carmona, E., Monet, F., Saad, F., Provencher, D., Mes-Masson, A.-M., et al. (2016) · Lab on a Chip · doi:10.1039/c5lc01108f · Cited by 182 · see citing works
Self-citationChitcholtan, K., Sykes, P. H., & Evans, J. J. (2012) · Journal of Translational Medicine · doi:10.1186/1479-5876-10-38 · Cited by 148 · see citing works
A novel 3D intestine barrier model to study the immune response upon exposure to microplastics
Lehner, R., Wohlleben, W., Septiadi, D., Landsiedel, R., Petri-Fink, A., & Rothen-Rutishauser, B. (2020) · Archives of Toxicology · doi:10.1007/s00204-020-02750-1 · Cited by 123 · see citing works
Zuchowska, A., Marciniak, K., Bazylinska, U., Jastrzebska, E., Wilk, K. A., & Brzozka, Z. (2018) · Sensors and Actuators B: Chemical · doi:10.1016/j.snb.2018.08.037 · Cited by 22 · see citing works
- Authors
- Zietarska, M., Maugard, C. M., Filali‐Mouhim, A., Alam‐Fahmy, M., Tonin, P. N., Provencher, D. M., & Mes‐Masson, A.
- Affiliations
- Centre Hospitalier de l’Université de Montréal (CA)
- McGill University Health Centre (CA)
- Corresponding author
- Mes‐Masson, Anne‐Marie
- Venue
- Molecular Carcinogenesis
- Publisher
- Wiley
- Published
- 2007-04-23
- Volume
- 46
- Issue
- 10
- Pages
- 872-885
- ISSN
- 0899-1987 (ISSN-L)
- 1098-2744
- OpenAlex
- W2093585643
- Cited by
- 209
- References
- 70
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 12 · 2023: 13 · 2022: 14 · 2021: 24 · 2020: 13 · 2019: 10 · 2018: 14 · 2017: 10 · 2016: 12 · 2015: 13 · 2014: 14 · 2013: 13 · 2012: 8
- FWCI
- 9.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Keywords
- epithelial ovarian cancer, 3D spheroid culture, in vitro tumor model, xenografts, monolayer culture, gene expression profiling, S100A6, tumor microenvironment, cell-cell interactions
- MeSH terms
- Animals, Epithelial Cells, Female, Humans, Models, Biological, Ovarian Neoplasms, Transplantation, Heterologous, Tumor Cells, Cultured, Spheroids, Cellular, Cell Culture Techniques, Gene Expression Profiling, Cell Line, Tumor, Tissue Array Analysis, Mice
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