Development and Angiographic Use of the Rabbit VX2 Model for Liver Cancer

Summary

The goal of this article is to provide a primer for the development and use of the VX2 carcinoma rabbit model for liver cancer.

Abstract

The rabbit VX2 tumor is an animal model commonly utilized for translational research regarding hepatocellular carcinoma (HCC) in the field of Interventional Radiology. This model employs an anaplastic squamous cell carcinoma that is easily and reliably propagated in the skeletal muscle of donor rabbits for eventual harvest and allograft implantation into the liver of naïve recipients. This tumor graft rapidly grows within the liver of recipient rabbits into an angiographically identifiable tumor characterized by a necrotic core surrounded by a viable hypervascular capsule. The physical size of the rabbit anatomy is sufficient to facilitate vascular instrumentation allowing for the application and testing of various interventional techniques. Despite these benefits, there exists a paucity of technical resources to act as a concrete reference for researchers working with the model. Herein, we present a comprehensive visual outline for the technical aspects of development, growth, propagation, and angiographic utilization of the rabbit VX2 tumor model for use by novice and experienced researchers alike.

Introduction

The rabbit VX2 tumor model has played a role in experimental oncology since its development in 1935^1,2. This tumor is a virus-induced anaplastic squamous cell carcinoma characterized by hypervascularity, rapid growth, and easy propagation in skeletal muscle^3,4. While the rabbit VX2 tumor model has been used to investigate a multitude of cancers^5,6,7,8; the focus of this paper is liver cancer⁹.

Protocol

The following protocol follows all requirements and guidelines mandated by the University of Illinois - Chicago. It was reviewed and approved by the local Institutional Animal Care and Use Committee prior to execution.

1. VX2 Hind Limb Tumor Development

1. Procure the VX2 tumor cell line from the National Cancer Institute Division of Cancer Treatment Diagnosis and Treatment Tumor/Cell Line Repository.
   Note: At this time, the order catalog can be found at the following link: https://dtp.cancer.gov/repositories/.
2. To prepare the cell suspension for injection, place the frozen VX2 sample and methylcellulose medium in l....

Results

When looking at Figure 1, it is clear that the quadricep of the rabbit is enlarged. Additionally, multiple small discrete nodules, typically correlating with tumor growth through the fascia, are visible. Upon palpation, the injected limb should appear than the non-injected limb. If a researcher requires more definitive assurance of tumor presence, ultrasound imaging can be used to identify the tumor embedded in the muscle. If a tumor is not detected, the hind.......

Discussion

The first critical step in the VX2 tumor methodology is successful propagation of a tumor in the hind limb of a donor rabbit. Refer to the first paragraph in the "Representative Results" section for more information regarding this step.

The next critical step is ensuring that the viable tumor capsule is properly identified. Not only will this be necessary for tumor suspension preparation, but it is also important for selecting and generating tumor pieces for hepatic implantation. The d.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
MethoCult (Methycellulose)	Stemcell Technologies	M3134
VX2 Cell Line	NCI	VX-2
5 mL Syringe	BD	309646
16 G Needle	BD	305197
22 G Needle	BD	305155
Hair Clippers	Wahl	41870-0438
Foam Insulated Box	Mr. Box Online	10 x 10 x 4
Acepromazine	Henry Schein	003845
Buprenorphine	Par	42023-179-05
Meloxicam	Henry Schein	049755
Alcohol Pads	Covidien	5033
Ketamine	Henry Schein	056344
Xylazine	Akorn	59399-110-20
Pentobarbital (Fatal-Plus)	Vortech	9373
Sterile Petri Dish	Thermo Fisher	172931
DMEM	Gibco	11965092
Saline	Baxter	2F7124
15-Blade	Steris	02-050-015
Scalpel Handle x 2	Steris	22-2381
Curved Hemostat	WPI	501288
Atraumatic Forceps	Sklar	52-5077
Gauze	Medline	NON21430LF
11-Blade	Steris	02-050-011
Surgicel	Ethicon	1951
3-0 PDS / Taper	Ethicon	Z305H
4 - 0 Vicryl / Cutting	Ethicon	J392H
40 μm strainer	BD	352340
50 mL conical tube	Thermo Fisher	339652
plastic pipette	Thomas Scientific	HS206371B
Centrifuge	Sorvall	75004240
1.40 mL Tubes (Internal Thread)	Micronic	MP32131-Z20
3-F VSI Micro-HV Introducer Kit	Vascular Solutions	Custom Order (P15180391)
.018 45° angle glidewire	Terumo	RG*GA1818SA
Direxion bern-shape microcatheter	Boston Scientific	M001195230
Omnipaque	GE	Y510