Identification of an easy to use 3D culture model to investigate invasion and anticancer drug response in chondrosarcomas.
Identification of an easy to use 3D culture model to investigate invasion and anticancer drug response in chondrosarcomas.
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DOI：
10.1186/s12885-017-3478-z
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发表时间：
2017-07-18
期刊：
影响因子：
3.8
通讯作者：
Baugé C
中科院分区：
文献类型：
--
作者：
Lhuissier E;Bazille C;Aury-Landas J;Girard N;Pontin J;Boittin M;Boumediene K;Baugé C
抗癌药物的细胞毒性功效已经用单层培养的癌细胞进行了广泛的研究。然而，药物在二维（2D）培养条件下的功效通常不同于三维（3D）培养条件。在本研究中，使用藻酸盐水凝胶构建体外肿瘤组织模型，并在软骨肉瘤中研究两种抗癌药物（顺铂和DZNep）的体外细胞毒性功效，并与体内反应进行比较。将来源于人软骨肉瘤的三种细胞系CH 2879、JJ 012和SW 1353包埋在藻酸盐水凝胶中。使用Cell Titer-Glo发光细胞活力测定试剂盒通过ATP测量并通过计数珠粒中的活细胞来测定增殖和存活。通过RT-PCR测定胶原和COMP的表达。通过计数离开藻酸盐珠和粘附于培养皿的细胞来估计侵袭/迁移。然后，软骨肉瘤对顺铂和DZNep的反应在单层培养或包埋在藻酸盐中的细胞之间进行比较，并在裸鼠中使用软骨肉瘤异种移植物。软骨肉瘤在藻酸盐包埋后至少存活8周。但只有CH 2879细胞能增殖。此外，该细胞系比SW 1353和JJ 012更具侵袭性，这与其各自原发性肿瘤的等级一致。此外，II型胶原的表达在软骨肉瘤中的3D培养高于2D。有趣的是，这种3D培养系统可以验证软骨肉瘤对顺铂的反应的缺乏，并预测DZNep在体内减少软骨肉瘤生长的效率。这项研究验证了藻酸盐珠作为一个相关的3D模型来研究癌症生物学和肿瘤对生物治疗的反应。
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. 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. 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. This study validates alginate beads as a relevant 3D model to study cancer biology and tumor responses to biological treatments.
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影响因子：
5
作者：
Monderer, David;Luseau, Alexandrine;Blanchard, Frederic
通讯作者：
Blanchard, Frederic
影响因子：
3.7
作者：
Leung, Matthew;Kievit, Forrest M.;Florczyk, Stephen J.;Veiseh, Omid;Wu, Jennifer;Park, James O.;Zhang, Miqin
通讯作者：
Zhang, Miqin
用于再生医学应用的海藻酸盐生物材料
DOI：
10.3390/ma6041285
发表时间：
2013-03-26
期刊：
Materials (Basel, Switzerland)
影响因子：
--
作者：
Sun J;Tan H
通讯作者：
Tan H
影响因子：
5
作者：
Gil-Benso, R;Lopez-Gines, C;Llombart-Bosch, A
通讯作者：
Llombart-Bosch, A
影响因子：
48
作者：
Fischbach, Claudia;Chen, Ruth;Mooney, David J.
通讯作者：
Mooney, David J.