AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Translational Res 2011;3(1):114-120

Original Article
Highly malignant intra-hepatic metastatic hepatocellular carcinoma in
rats

Yang Guo, Rachel Klein, Reed A. Omary, Guang-Yu Yang,  Andrew C. Larson

Department of Radiology, Northwestern University, Chicago, IL, 60611, USA; Robert H. Lurie Comprehensive
Cancer Center, Chicago, IL, 60611, USA; Department of Biomedical Engineering, Northwestern University,
Evanston, IL, 60208, USA; Department of Pathology, Northwestern University, Chicago, IL, 60611, USA.

Received October 25, 2010; Accepted October, 2010; Epub October, Published January 1, 2011

Abstract: Intra-hepatic metastasis is one of the major modalities that lead to the recurrence of advanced HCC.
Research efforts to investigate HCC metastasis/recurrence and therapy response will require appropriate
models. For our study, the main purpose was to compare two different rodent syngenic orthotopic HCC models
using MRI and pathologic evidence; we specifically sought to investigate the intra-hepatic metastatic properties of
HCC in Buffalo rats. Methods: 12 female Buffalo rats and 16 male Sprague Dawley (SD) rats were used in these
studies. Subcapsular implantation of 1×106 McA-RH7777 and 1×106 N1-S1 rat hepatoma cells into the left
hepatic lobe was carried out in Buffalo and SD rats, respectively. Buffalo hepatoma rats (n=5/6) and SD hepatoma
rats (n=6/8) were imaged using MRI at 6-8 days after implantation. Then, another group of Buffalo HCC rats
(n=6/6) and SD HCC (n=6/8) rats were scanned at 21-25 days interval post-implantation. After image acquisition,
tumor sections were evaluated with H&E and CD34 staining. Results: Tumor induction rat for Buffalo rats was
92% (11/12) compared to 75% (12/16) for SD rats. The mean tumor size of McA-RH7777 hepatoma rats at 6-8
day interval was 1.32±0.56cm, but progressed to multiple intra-hepatic metastasis at 21-25 day interval in 6/6 rats
(100%). In contrast, the mean tumor size of N1-S1 rats at early interval was 1.06±0.32cm, these progressed to
only a single solid mass of 2.35±0.69cm at later interval without obvious intra-hepatic metastasis. H&E staining
showed that McA-RH7777 cell induced Morris hepatoma exhibited typical trabecular growth pattern, better
representative of human HCC compared to the sheet pattern of N1-S1 cell induced Novikoff hepatoma.
Conclusion: The McA-Rh7777 rat hepatoma model was demonstrated to be a highly malignant intra-hepatic
metastasis model of potential utility for HCC research.  (AJTR1010004).

Keywords: Hepatocellular carcinoma (HCC), rodent model, orthotopic implantation, N1-S1 rat HCC cell line,
McA-RH7777 rat HCC cell line, MRI, histopathology.

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Address all correspondence to:
Andrew C. Larson, PhD
Departments of Radiology and Biomedical Engineering
Northwestern University Feinberg School of Medicine
737 N. Michigan Ave, 16th Floor, Chicago, IL 60611, USA
Tel: + 01-1-3129263499, Fax: +01-1-3129265991
E-mail:
a-larson@northwestern.edu