Rabbit VX2 lung tumor models can form early nodal metastases

Abstract

BackgroundThe 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.MethodsRabbit 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.ResultsNodal 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.ConclusionsRabbit 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.

Establishing a novel model of malignant airway stenosis in rabbit

“…The VX2 tumor, a squamous cell cancer model, which was firstly proposed by Shope and Hurst ( 12 ) in 1933, has been implanted in many sites of rabbits, including the liver, kidney, lung, esophagus, and muscle ( 13 – 15 ). Although the rabbits belong to moderate-to-large-sized models and have been used to study benign airway stenosis in stent-related research ( 16 , 17 ), there have been no reports on establishing a rabbit model with malignant airway stenosis.…”

A preclinical research platform to evaluate photosensitizers for transbronchial localization and phototherapy of lung cancer using an orthotopic mouse model

“…In mid-sized animals, a common orthotopic lung tumor model is the VX2 rabbit model. VX2 tumor-bearing models are able to form large primary tumors that closely imitate human lung cancer growth and metastasis (18). However, VX2 cells are not human lung cancer, instead being derived from a rabbit virus-induced papilloma (19).…”