Osteosarcoma (OS) is the most common primary malignant tumor of bone, which preferentially develops lung metastasis. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for patients with metastatic or recurrent OS remains dramatically poor. Novel therapies are therefore required to slow progression and eradicate the disease. Furthermore, to better understand the cellular and molecular mechanisms responsible for OS onset and progression, the development of novel predictive culture systems resembling the native three-dimensional (3D) tumor microenvironment are mandatory. ‘Tumor engineering’ approaches radically changed the previous scenario, through the development of advanced and alternative 3D cell culture in vitro models able to tightly mimic the in vivo tumor microenvironment.
In this review, we will summarize the state of the art in this novel area, illustrating the different methods and techniques employed to realize 3D OS cell culture models and we report the achieved results, which highlight the efficacy of these models in reproducing the tumor milieu. Although data need to be further validated, the scientific studies reviewed here are certainly promising and give new insights into the clinical practice.
Alessio N, Capasso S, Di Bernardo G, Cappabianca S, Casale F, Calarco A, Cipollaro M, Peluso G, Galderisi U. Mesenchymal stromal cells having inactivated RB1 survive following low irradiation and accumulate damaged DNA: hints for side effects following radiotherapy. Cell Cycle. 2017;16(3):251–8. CrossRefPubMed
Ghajar CM, Bissell MJ. Tumor engineering: the other face of tissue engineering. Tissue Eng A. 2010;16(7):2153–6. CrossRef
Vinci M, Gowan S, Boxall F, Patterson L, Zimmermann M, Court W, Lomas C, Mendiola M, Hardisson D, Eccles SA. Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation. BMC Biol. 2012;10:29. CrossRefPubMedPubMedCentral
Indovina P, Rainaldi G, Santini MT. Hypoxia increases adhesion and spreading of MG-63 three-dimensional tumor spheroids. Anticancer Res. 2008;28(2A):1013–22. PubMed
Guo XD, Yu L, Zhang ZP, Dai G, Gao T, Guo W. miR-335 negatively regulates osteosarcoma stem cell-like properties by targeting POU5F1. Cancer Cell Int. 2017;17:29.
Amann A, Zwierzina M, Gamerith G, Bitsche M, Huber JM, Vogel GF, Blumer M, Koeck S, Pechriggl EJ, Kelm JM, Hilbe W, Zwierzina H. Development of an Innovative 3D Cell Culture System to Study Tumour-Stroma Interactions in Non-Small Cell Lung Cancer Cells. PLoS One. 2014;9(3).
Rubio R, Abarrategi A, Garcia-Castro J, Martinez-Cruzado L, Suarez C, Tornin J, Santos L, Astudillo A, Colmenero I, Mulero F, Rosu-Myles M, Menendez P, Rodriguez R. Bone environment is essential for Osteosarcoma development from transformed Mesenchymal stem cells. Stem Cells. 2014;32(5):1136–48. CrossRefPubMed
Di Fiore R, Drago-Ferrante R, Pentimalli F, Di Marzo D, Forte IM, D'Anneo A, Carlisi D, De Blasio A, Giuliano M, Tesoriere G, Giordano A, Vento R. MicroRNA-29b-1 impairs in vitro cell proliferation, self-renewal and chemoresistance of human osteosarcoma 3AB-OS cancer stem cells. Int J Oncol. 2014;45(5):2013–23. CrossRefPubMedPubMedCentral
Techavichit P, Gao Y, Kurenbekova L, Shuck R, Donehower LA, Yustein JT. Secreted Frizzled-Related Protein 2 (sFRP2) promotes osteosarcoma invasion and metastatic potential. BMC Cancer. 2016;16(1):869.
Fu D, He X, Yang S, Xu W, Lin T, Feng X. Zoledronic acid inhibits vasculogenic mimicry in murine osteosarcoma cell line in vitro. BMC Musculoskelet Disord. 2011;12:146.
Fallica B, Maffei JS, Villa S, Makin G, Zaman M. Alteration of cellular behavior and response to PI3K pathway inhibition by culture in 3D collagen gels. PLoS One. 2012;7(10):e48024.
Tan PHS, Chia SS, Toh SL, Goh JCH, Nathan SS. The dominant role of IL-8 as an Angiogenic driver in a three-dimensional physiological tumor construct for drug testing. Tissue Eng A. 2014;20(11–12):1758–66. CrossRef
E. Jabbari, S. K. Sarvestani, L. Daneshian and S. Moeinzadeh, "Optimum 3D Matrix Stiffness for Maintenance of Cancer Stem Cells Is Dependent on Tissue Origin of Cancer Cells," PLoS One, vol. 10, no. 7, 2015.
R. Bartlett, W. Everett, S. Lim, N. G, M. Loizidou, G. Jell, A. Tan and A. M. Seifalian, "Personalized in vitro cancer modeling - fantasy or reality?," Transl Oncol, vol. 7, no. 6, pp. 657-664, 2014.
M. Zanoni, F. Piccinini, C. Arienti, A. Zamagni, S. Santi, R. Polico, A. Bevilacqua and A. Tesei, "3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained," Scientific Reports, vol. 6, 2016.
Halfter K, Mayer B. Bringing 3D tumor models to the clinic - predictive value for personalized medicine. Biotechnol J. 2017;12(2).
Herter S, Morra L, Schlenker R, Sulcova J, Fahrni L, Waldhauer I, Lehmann S, Reislander T, Agarkova I, Kelm JM, Klein C, Umana P, Bacac M. A novel three-dimensional heterotypic spheroid model for the assessment of the activity of cancer immunotherapy agents. Cancer Immunol Immunother. 2017;66(1):129–40. CrossRefPubMed
M. Upreti, A. Jamshidi-Parsian, N. A. Koonce, J. S. Webber, S. K. Sharma, A. A. A. Asea, M. J. Mader and R. J. Griffin, "Tumor-endothelial cell three-dimensional spheroids: new aspects to enhance radiation and drug therapeutics," Transl Oncol, vol. 4, no. 6, pp. 365-U138, 2011.
Weeber F, van de Wetering M, Hoogstraat M, Dijkstra KK, Krijgsman O, Kuilman T, Gadellaa-van Hooijdonk CG, van der Velden DL, Peeper DS, Cuppen EP, Vries RG, Clevers H, Voest EE. Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases. Proc Natl Acad Sci U S A. 2015;112(43):13308–11. CrossRefPubMedPubMedCentral
- Relevance of 3d culture systems to study osteosarcoma environment
Angela De Luca
- BioMed Central
Journal of Experimental & Clinical Cancer Research
Elektronische ISSN: 1756-9966
Neu im Fachgebiet Onkologie
Mail Icon II