Abstract
BackgroundCytotoxic 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.MethodsThree 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.ResultsChondrosarcomas 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.ConclusionsThis study validates alginate beads as a relevant 3D model to study cancer biology and tumor responses to biological treatments.
Highlights
Cytotoxic efficacy of anticancer drugs has been widely studied with monolayer-cultured cancer cells
That is why we looked for another 3D culture which does not require the addition of growth factors, but which allows chondrogenic differentiation and provide a pathophysiological context that could replicate the chondrosarcoma microenvironment compared to monolayer cultures in 2D system
We evaluated the use of this 3D culture system to study chondrosarcoma biology and predict drug response
Summary
Cytotoxic efficacy of anticancer drugs has been widely studied with monolayer-cultured cancer cells. 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. Chondrosarcoma (CHS) is a malignant tumor characterized by the presence of a cartilaginous extracellular matrix. Most studies aiming to investigate chondrosarcoma biology and response to anticancer drugs are done using chondrosarcoma cell lines cultured in monolayer. Whereas this method is useful to understand some processes and mechanisms, it often fails to mimic the natural tumor microenvironment, which is an important parameter in tumor signaling and drug response [7, 8]. The traditional 2D cell cultures cannot ideally recapitulate in vivo physiological conditions [6, 11]
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