Division of Thoracic Surgery, Toronto General Hospital, University Health Network, 200 Elizabeth St, 9N-957, Toronto, ON, M5G2C4, Canada.
World J Surg Oncol. 2019 Dec 29;17(1):231. doi: 10.1186/s12957-019-1774-6.
The rabbit squamous cell cancer line, VX2, has been used to generate various tumor models in rabbits. It is notable for its ability to generate nodal metastases. However, the timing and extent of nodal metastases vary by primary inoculation site and methodology. The development of metastases specifically in lung cancer models has not been well-described. We sought to characterize the generation of nodal metastases in rabbit transbronchial VX2 lung tumor models.
Rabbit VX2 lung tumor models were created in the right lung via transbronchial injection and serially imaged by computed tomography. Rabbits (n = 15) were sacrificed from between 5 and 24 days post-inoculation for collection of the ipsilateral and contralateral paratracheal lymph nodes. These underwent histopathological evaluation for metastases using hematoxylin and eosin as well as cytokeratin AE1/AE3 immunohistochemical staining.
Nodal metastases were detectable as early as 1 week after inoculation but were more prevalent with longer inoculation; all rabbits at > 2 weeks post-inoculation had nodal metastases. Contralateral metastases were in general seen later than ipsilateral metastases. Lymph node volume did not predict the likelihood of nodal metastases (p = 0.4 and p = 0.07 for ipsilateral and contralateral nodal metastases, respectively), but primary tumor volume was significantly associated with the likelihood of nodal metastases (p = 0.001 and p = 0.005 for ipsilateral and contralateral nodal metastases, respectively). Ipsilateral metastases were detectable at a tumor diameter of 1 cm; contralateral metastases were more variable but in general required a tumor diameter of 2 cm.
Rabbit transbronchial VX2 lung tumor models generate nodal metastases relatively early after inoculation. These results suggest such models may be valuable tools in the investigation of novel therapeutic modalities relevant for the treatment of both early-stage and locally advanced lung cancer.
兔鳞状细胞癌 VX2 株已被用于在兔体内生成各种肿瘤模型。其特点是能够产生淋巴结转移。然而，原发接种部位和方法的不同，淋巴结转移的时间和范围也不同。在肺癌模型中，转移瘤的发生发展情况尚未得到充分描述。本研究旨在探讨兔经支气管 VX2 肺癌模型中淋巴结转移的发生情况。
通过经支气管注射在右肺中建立兔 VX2 肺癌模型，并通过计算机断层扫描进行连续成像。在接种后 5 至 24 天内处死兔子（n = 15），采集同侧和对侧气管旁淋巴结。使用苏木精和伊红（H&E）以及细胞角蛋白 AE1/AE3 免疫组织化学染色对转移瘤进行组织病理学评估。
接种后 1 周即可检测到淋巴结转移，但接种时间越长，转移越普遍；所有接种>2 周的兔子均有淋巴结转移。对侧转移一般比同侧转移晚出现。淋巴结体积与淋巴结转移的可能性无相关性（同侧和对侧淋巴结转移的 p 值分别为 0.4 和 0.07），但原发肿瘤体积与淋巴结转移的可能性显著相关（同侧和对侧淋巴结转移的 p 值分别为 0.001 和 0.005）。同侧转移瘤可在肿瘤直径 1cm 时检测到；对侧转移瘤的发生更具变异性，但通常需要肿瘤直径 2cm。
兔经支气管 VX2 肺癌模型在接种后相对较早地产生淋巴结转移。这些结果表明，此类模型可能是研究针对早期和局部晚期肺癌的新型治疗方法的有价值的工具。
