Department of Thoracic and Head and Neck Medical Oncology, Sheba Medical Center, Sheba, Israel.
J Thorac Oncol. 2013 Feb;8(2):140-6. doi: 10.1097/JTO.0b013e3182725ff9.
Although subcutaneous xenograft models have been widely used to evaluate the antitumor activity of new compounds, these models present a major disadvantage because the tumors do not accurately represent the cancer biology, especially with regard to metastasis and drug sensitivity. Effective murine models of small-cell lung cancer (SCLC) are needed.
To provide strategies for studying new therapies and tumor biology, we developed three orthotopic models of human SCLC (H69A, a variant of the National Cancer Institute [NCI]-H69 cell line selected for invasiveness in vitro, NCI-H187, and NCI-N417) in nude mice. Tumor cells were injected into their lungs and new cell lines were established from these tumors (H69ALu, H187Lu, and N417Lu) to select for a reproducible tumor growth pattern and minimize variations in tumor size.
In all three models tumors started as a solitary mass in the left lung and spread to mediastinal and axillary lymph nodes and to the right lung in a pattern similar to that observed in human SCLC. To test the accuracy of this model in representing SCLC as seen in the clinic, we compared the efficacy of chemotherapeutic agents in each model. Irinotecan significantly inhibited the growth and progression of all three human SCLC tumors, and cisplatin, paclitaxel, and etoposide significantly inhibited the growth and progression of H69ALu tumors over the control agent.
We have established three orthotopic murine models of human SCLC closely resembling the course of human SCLC seen in the clinic including metastasis to lymph nodes and distant organs. They provide a means for better understanding the biology of this disease and will enable evaluation of novel therapeutic strategies.
尽管皮下异种移植模型已被广泛用于评估新化合物的抗肿瘤活性，但这些模型存在一个主要缺点，因为肿瘤不能准确地代表癌症生物学，尤其是在转移和药物敏感性方面。需要有效的小细胞肺癌（SCLC）的小鼠模型。
为了为新疗法和肿瘤生物学的研究提供策略，我们在裸鼠中建立了三种人 SCLC（H69A，一种选择用于体外侵袭性的 NCI-H69 细胞系变体，NCI-H187 和 NCI-N417）的原位模型。将肿瘤细胞注入其肺部，并从这些肿瘤中建立新的细胞系（H69ALu、H187Lu 和 N417Lu），以选择可重现的肿瘤生长模式并最大程度地减少肿瘤大小的变化。
在所有三种模型中，肿瘤均开始在左肺中形成单一肿块，并扩散至纵隔和腋窝淋巴结，然后像在人 SCLC 中观察到的那样扩散至右肺。为了测试该模型在代表临床所见 SCLC 方面的准确性，我们比较了每个模型中化疗药物的疗效。伊立替康显著抑制了所有三种人 SCLC 肿瘤的生长和进展，顺铂、紫杉醇和依托泊苷显著抑制了 H69ALu 肿瘤的生长和进展，优于对照药物。
我们已经建立了三种与人 SCLC 非常相似的人 SCLC 原位小鼠模型，包括淋巴结和远处器官的转移。它们为更好地了解这种疾病的生物学提供了一种手段，并将能够评估新的治疗策略。
