Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Identification of an easy to use 3D culture model to investigate invasion and anticancer drug response in chondrosarcomas

Authors: Eva Lhuissier, Céline Bazille, Juliette Aury-Landas, Nicolas Girard, Julien Pontin, Martine Boittin, Karim Boumediene, Catherine Baugé

Published in: BMC Cancer | Issue 1/2017

Login to get access

Abstract

Background

Cytotoxic efficacy of anticancer drugs has been widely studied with monolayer-cultured cancer cells. However, the efficacy of drugs under two-dimensional (2D) culture condition usually differs from that of three-dimensional (3D) one. In the present study, an in vitro tumor tissue model was constructed using alginate hydrogel, and in vitro cytotoxic efficacy of two anticancer drugs (cisplatin and DZNep) was investigated in chondrosarcomas, and compared to in vivo response.

Methods

Three cell lines derived from human chondrosarcomas, CH2879, JJ012 and SW1353, were embedded in alginate hydrogel. Proliferation and survival were assayed by ATP measurement using Cell Titer-Glo luminescent cell viability assay kit, and by counting viable cells in beads. Collagen and COMP expression was determined by RT-PCR. Invasion/migration was estimated by counting cells leaving alginate beads and adhering to culture dish. Then, chondrosarcoma response to cisplatin and DZNep was compared between cells cultured in monolayer or embedded in alginate, and using chondrosarcoma xenografts in nude mice.

Results

Chondrosarcomas survived at least for 8 weeks, after embedment in alginate. However, only CH2879 cells could proliferate. Also, this cell line is more invasive than SW1353 and JJ012, which was coherent with the grade of their respective primary tumors. Furthermore, the expression of type II collagen was higher in chondrosarcomas cultured in 3D than in 2D. Interestingly, this 3D culture system allows to validate the absence of response of chondrosarcomas to cisplatin, and to predict the efficiency of DZNep to reduce chondrosarcoma growth in vivo.

Conclusions

This study validates alginate beads as a relevant 3D model to study cancer biology and tumor responses to biological treatments.
Literature
1.
Nota SPFT, Braun Y, Schwab JH, van Dijk CN, Bramer JAM. The identification of prognostic factors and survival statistics of conventional central chondrosarcoma. Sarcoma. 2015;2015 doi:10.​1155/​2015/​623746.
2.
Bovée JV, Cleton-Jansen A-M, Taminiau AH, Hogendoorn PC. Emerging pathways in the development of chondrosarcoma of bone and implications for targeted treatment. Lancet Oncol. 2005;6:599–607.CrossRefPubMed
3.
Samuel AM, Costa J, Lindskog DM. Genetic alterations in chondrosarcomas - keys to targeted therapies? Cell Oncol Dordr. 2014;37:95–105.CrossRefPubMed
4.
Van Oosterwijk JG, Herpers B, Meijer D, Briaire-de Bruijn IH, Cleton-Jansen AM, Gelderblom H, et al. Restoration of chemosensitivity for doxorubicin and cisplatin in chondrosarcoma in vitro: BCL-2 family members cause chemoresistance. Ann Oncol Off J Eur Soc Med Oncol ESMO. 2012;23:1617–26.CrossRef
5.
Bovée JVMG, Hogendoorn PCW, Wunder JS, Alman BA. Cartilage tumours and bone development: molecular pathology and possible therapeutic targets. Nat Rev Cancer. 2010;10:481–8.CrossRefPubMed
6.
Monderer D, Luseau A, Bellec A, David E, Ponsolle S, Saiagh S, et al. New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance. Lab Investig J Tech Methods Pathol. 2013;93:1100–14.CrossRef
7.
Ekert JE, Johnson K, Strake B, Pardinas J, Jarantow S, Perkinson R, et al. Three-dimensional lung tumor microenvironment modulates therapeutic compound responsiveness in vitro – implication for drug development. PLoS One. 2014;9:e92248.CrossRefPubMedPubMedCentral
8.
Weigelt B, Ghajar CM, Bissell MJ. The need for complex 3D culture models to unravel novel pathways and identify accurate biomarkers in breast cancer. Adv Drug Deliv Rev 2014;0:42–51.
9.
Kramer N, Walzl A, Unger C, Rosner M, Krupitza G, Hengstschläger M, et al. In vitro cell migration and invasion assays. Mutat Res. 2013;752:10–24.CrossRefPubMed
10.
Chen L, Xiao Z, Meng Y, Zhao Y, Han J, Su G, et al. The enhancement of cancer stem cell properties of MCF-7 cells in 3D collagen scaffolds for modeling of cancer and anti-cancer drugs. Biomaterials. 2012;33:1437–44.CrossRefPubMed
11.
Becker JL, Blanchard DK. Characterization of primary breast carcinomas grown in three-dimensional cultures. J Surg Res. 2007;142:256–62.CrossRefPubMed
12.
Kim JB. Three-dimensional tissue culture models in cancer biology. Semin Cancer Biol. 2005;15:365–77.CrossRefPubMed
13.
14.
Fischbach C, Chen R, Matsumoto T, Schmelzle T, Brugge JS, Polverini PJ, et al. Engineering tumors with 3D scaffolds. Nat Methods. 2007;4:855–60.CrossRefPubMed
15.
Leung M, Kievit FM, Florczyk SJ, Veiseh O, Wu J, Park JO, et al. Chitosan-alginate scaffold culture system for hepatocellular carcinoma increases malignancy and drug resistance. Pharm Res. 2010;27:1939–48.CrossRefPubMedPubMedCentral
16.
Dit Faute MA, Laurent L, Ploton D, Poupon M-F, Jardillier J-C, Bobichon H. Distinctive alterations of invasiveness, drug resistance and cell-cell organization in 3D-cultures of MCF-7, a human breast cancer cell line, and its multidrug resistant variant. Clin Exp Metastasis. 2002;19:161–8.CrossRefPubMed
17.
Halfter K, Mayer B. Bringing 3D tumor models to the clinic - predictive value for personalized medicine. Biotechnol J. 2017;12
18.
Santo VE, Rebelo SP, Estrada MF, Alves PM, Boghaert E, Brito C. Drug screening in 3D in vitro tumor models: overcoming current pitfalls of efficacy read-outs. Biotechnol J. 2017;12
19.
Horman SR, Hogan C, Delos Reyes K, Lo F, Antczak C. Challenges and opportunities toward enabling phenotypic screening of complex and 3D cell models. Future Med Chem. 2015;7:513–25.CrossRefPubMed
20.
Duval E, Leclercq S, Elissalde J-M, Demoor M, Galéra P, Boumédiene K. Hypoxia-inducible factor 1α inhibits the fibroblast-like markers type I and type III collagen during hypoxia-induced chondrocyte redifferentiation: hypoxia not only induces type II collagen and aggrecan, but it also inhibits type I and type III collagen in the hypoxia-inducible factor 1α–dependent redifferentiation of chondrocytes. Arthritis Rheum. 2009;60:3038–48.CrossRefPubMed
21.
Duval E, Baugé C, Andriamanalijaona R, Bénateau H, Leclercq S, Dutoit S, et al. Molecular mechanism of hypoxia-induced chondrogenesis and its application in in vivo cartilage tissue engineering. Biomaterials. 2012;33:6042–51.CrossRefPubMed
22.
Duval E, Bigot N, Hervieu M, Kou I, Leclercq S, Galéra P, et al. Asporin expression is highly regulated in human chondrocytes. Mol Med Camb Mass. 2011;17:816–23.PubMedPubMedCentral
23.
Andriamanalijaona R, Duval E, Raoudi M, Lecourt S, Vilquin JT, Marolleau JP, et al. Differentiation potential of human muscle-derived cells towards chondrogenic phenotype in alginate beads culture. Osteoarthr Cartil OARS Osteoarthr Res Soc. 2008;16:1509–18.CrossRef
24.
Bonaventure J, Kadhom N, Cohen-Solal L, Ng KH, Bourguignon J, Lasselin C, et al. Reexpression of cartilage-specific genes by dedifferentiated human articular chondrocytes cultured in alginate beads. Exp Cell Res. 1994;212:97–104.CrossRefPubMed
25.
Perets A, Baruch Y, Weisbuch F, Shoshany G, Neufeld G, Cohen S. Enhancing the vascularization of three-dimensional porous alginate scaffolds by incorporating controlled release basic fibroblast growth factor microspheres. J Biomed Mater Res A. 2003;65A:489–97.CrossRef
26.
Sun J, Tan H. Alginate-based biomaterials for regenerative medicine applications. Materials. 2013;6:1285–309.CrossRef
27.
Gil-Benso R, Lopez-Gines C, Lopez-Guerrero JA, Carda C, Callaghan RC, Navarro S, et al. Establishment and Characterization of a Continuous Human Chondrosarcoma Cell Line, ch-2879: Comparative Histologic and Genetic Studies with Its Tumor of Origin. Lab Invest. 83:877–87.
28.
Scully SP, Berend KR, Toth A, Qi WN, Qi Z, Block JA. Marshall Urist Award. Interstitial collagenase gene expression correlates with in vitro invasion in human chondrosarcoma. Clin Orthop. 2000:291–303.
29.
Girard N, Bazille C, Lhuissier E, Benateau H, Llombart-Bosch A, Boumediene K, et al. 3-deazaneplanocin a (DZNep), an inhibitor of the histone methyltransferase EZH2, Induces Apoptosis and Reduces Cell Migration in Chondrosarcoma Cells. PLoS ONE. 2014;9:e98176.CrossRefPubMedPubMedCentral
30.
Baugé C, Bazille C, Girard N, Lhuissier E, Boumediene K. Histone methylases as novel drug targets: developing inhibitors of EZH2. Future Med Chem. 2014;6:1943–65.CrossRefPubMed
31.
Mafi P, Hindocha S, Mafi R, Khan WS. Evaluation of biological protein-based collagen scaffolds in cartilage and musculoskeletal tissue engineering--a systematic review of the literature. Curr Stem Cell Res Ther. 2012;7:302–9.CrossRefPubMed
32.
33.
Estrada MF, Rebelo SP, Davies EJ, Pinto MT, Pereira H, Santo VE, et al. Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression. Biomaterials. 2016;78:50–61.CrossRefPubMed
34.
35.
Wu H-M, Jiang Z-F, Ding P-S, Shao L-J, Liu R-Y. Hypoxia-induced autophagy mediates cisplatin resistance in lung cancer cells. Sci Rep. 2015;5 doi:10.​1038/​srep12291.
Metadata
Title
Identification of an easy to use 3D culture model to investigate invasion and anticancer drug response in chondrosarcomas
Authors
Eva Lhuissier
Céline Bazille
Juliette Aury-Landas
Nicolas Girard
Julien Pontin
Martine Boittin
Karim Boumediene
Catherine Baugé
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3478-z

Other articles of this Issue 1/2017

BMC Cancer 1/2017 Go to the issue

Research article

EMX2 gene expression predicts liver metastasis and survival in colorectal cancer

Research article

Precision medicine approaches to lung adenocarcinoma with concomitant MET and HER2 amplification

Research article

Timing of chemotherapy-induced neutropenia predicts prognosis in metastatic colon cancer patients: a retrospective study in mFOLFOX6 -treated patients

Research article

Process quality of decision-making in multidisciplinary cancer team meetings: a structured observational study

Database

King’s Health Partners’ Prostate Cancer Biobank (KHP PCaBB)

Research article

Common variants in glucuronidation enzymes and membrane transporters as potential risk factors for colorectal cancer: a case control study
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits