Use of osteoblast-derived matrix to assess the influence of collagen modifications on cancer cells.
Use of osteoblast-derived matrix to assess the influence of collagen modifications on cancer cells.
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DOI：
10.1016/j.mbplus.2020.100047
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发表时间：
2020-11
影响因子：
--
通讯作者：
Kurie JM
中科院分区：
文献类型：
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作者：
Bota-Rabassedas N;Guo HF;Banerjee P;Chen Y;Terajima M;Yamauchi M;Kurie JM
胶原间质积聚预示多种恶性肿瘤的临床预后较差。需要更好的工具来阐明胶原蛋白影响癌细胞的方式。在这里，我们报告了一种方法来产生胶原基质，缺乏关键的翻译后修饰，并评估癌细胞在这些基质上的行为。我们利用遗传和生物化学方法来抑制MC-3 T3-E1小鼠成骨细胞（MC细胞）产生的胶原蛋白上的赖氨酸羟基化和葡萄糖基化。接种到MC细胞衍生的基质表面上，含有单独的肺腺癌细胞或与癌症相关的成纤维细胞组合的多细胞聚集体以受胶原修饰影响的时间和空间模式解离。这些发现证明了产生适用于细胞培养研究的限定胶原基质的可行性。在具有确定的胶原修饰的基质上培养多细胞聚集体的可行性。胶原蛋白修饰影响癌细胞行为。这种方法对癌症研究人员来说是一种有用的工具。
Collagenous stromal accumulations predict a worse clinical outcome in a variety of malignancies. Better tools are needed to elucidate the way in which collagen influences cancer cells. Here, we report a method to generate collagenous matrices that are deficient in key post-translational modifications and evaluate cancer cell behaviors on those matrices. We utilized genetic and biochemical approaches to inhibit lysine hydroxylation and glucosylation on collagen produced by MC-3T3-E1 murine osteoblasts (MC cells). Seeded onto MC cell-derived matrix surface, multicellular aggregates containing lung adenocarcinoma cells alone or in combination with cancer-associated fibroblasts dissociated with temporal and spatial patterns that were influenced by collagen modifications. These findings demonstrate the feasibility of generating defined collagen matrices that are suitable for cell culture studies. Feasibility of culturing multicellular aggregates on matrices with defined collagen modifications. Collagen modifications influence cancer cell behavior. This methodology is a useful tool for cancer researchers.