The microenvironment plays a major role in conferring chemoresistance to cancer cells. In order to better inform clinical response to chemoresistance, preclinical models that recapitulate its hallmark features are needed to enable screening for resistance-specific therapeutic targets. A novel platform for seeding cancer cells in 3D hydrogels is presented utilizing derivatives of chitosan and alginate that, critically, is amenable to high throughput screening: cell seeding in hydrogels, media changes, dosing of anticancer compounds, and cell viability assays are all automated using a standard and commercially available liquid handling robot. Culture in these hydrogels elicits resistance in ovarian, lung, and prostate cancer cells to treatment by doxorubicin and paclitaxel. In correlation, proteomics analysis of SKOV3 cells cultured in 3D reveals enrichment of proteins associated with extreme drug resistance including HMOX1 and ALDH2. Subsequently, therapeutic antibodies targeted to tumor-associated antigens upregulated in 3D cultures are shown to have higher efficacy compared to 2D cultures. Collectively, this automated 3D cell culture platform provides a powerful tool with utility in identification of drugs that may overcome chemoresistance.

中文翻译：

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一个自动化的水凝胶培养平台，用于评估基于抗体的药物在克服化学耐药性方面的功效。

微环境在赋予癌细胞化学抗性中起主要作用。为了更好地告知对化学抗药性的临床反应，需要概括其标志性特征的临床前模型来筛选抗药性特异性治疗靶标。提出了一种利用壳聚糖和藻酸盐衍生物在3D水凝胶中接种癌细胞的新型平台，该平台至关重要地适用于高通量筛选：水凝胶中的细胞接种，培养基变化，抗癌化合物的剂量以及细胞活力测定都可以通过以下方法实现自动化标准的市售液体处理机器人。这些水凝胶中的培养物在卵巢，肺癌和前列腺癌细胞中引起对阿霉素和紫杉醇治疗的耐药性。相关地，对以3D模式培养的SKOV3细胞进行的蛋白质组学分析显示，与极端耐药相关的蛋白质（包括HMOX1和ALDH2）富集。随后，与2D培养相比，针对3D培养中上调的肿瘤相关抗原的治疗性抗体具有更高的疗效。总的来说，这个自动化的3D细胞培养平台提供了强大的工具，可用于识别可能克服化学抗性的药物。