Departments of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
J Thorac Oncol. 2013 Feb;8(2):131-9. doi: 10.1097/JTO.0b013e3182779ccf.
Primary culture of cancer cells is expected to be useful for investigating the biology of cancer and predicting chemosensitivity for individual patients, yet has been hampered by technical difficulties. We recently developed the cancer tissue-originated spheroid (CTOS) method for the primary culture of colorectal cancer cells. In the present study, we applied this system to the primary culture of non-small-cell lung cancer.
We used 125 surgical specimens and 18 pleural effusions for CTOS preparation. Partially digested tumor fragments were cultured in a medium for embryonic stem cells. CTOSs were subjected to sensitivity assay and signal transduction assay for the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib. We also investigated the effects of growth factors in culturing lung cancer CTOS.
The success rate of CTOS preparation from surgical specimens was 80.0%. The CTOS method was also suitable for culturing tumor spheroids from pleural effusions. CTOSs from lung cancer consisted mostly of pure cancer cells. CTOSs and CTOS-derived xenografts retained the characteristics of the original tumors. In vitro assay results showed that EGFR mutation status and expression levels corresponded with erlotinib sensitivity, confirming previous clinical findings. Furthermore, we found that neuregulin 1, a ligand of HER3, potently induced CTOS growth.
The CTOS method enables us to obtain primary lung tumor cells of high viability and purity. CTOS could be a new platform for studying lung cancer biology.
原代培养癌细胞有望用于研究癌症生物学和预测个体患者的化疗敏感性，但一直受到技术困难的阻碍。我们最近开发了用于结直肠癌细胞原代培养的癌症组织起源球体（CTOS）方法。在本研究中，我们将该系统应用于非小细胞肺癌的原代培养。
我们使用 125 个手术标本和 18 个胸腔积液进行 CTOS 准备。部分消化的肿瘤片段在胚胎干细胞培养基中培养。对 CTOS 进行表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）厄洛替尼的敏感性测定和信号转导测定。我们还研究了生长因子在培养肺癌 CTOS 中的作用。
手术标本 CTOS 制备的成功率为 80.0%。CTOS 方法也适用于培养胸腔积液中的肿瘤球体。来自肺癌的 CTOS 主要由纯癌细胞组成。CTOS 和 CTOS 衍生的异种移植物保留了原始肿瘤的特征。体外检测结果表明，EGFR 突变状态和表达水平与厄洛替尼敏感性相对应，证实了先前的临床发现。此外，我们发现神经调节蛋白 1（HER3 的配体）可强力诱导 CTOS 生长。
CTOS 方法使我们能够获得高活力和高纯度的原代肺肿瘤细胞。CTOS 可能成为研究肺癌生物学的新平台。
