Published in Cancer Detection and Prevention 2001; 25(5):439-445.

Expression of L-Type Amino Acid Transporter 1 in a Rat Model of Liver Metastasis: Positive Correlation with Tumor Size

Satoru Tamal, MD,a Hideki Masuda, MD,a Yukimoto Ishii, MD,a Shigeru Suzuki, MD,a Yoshikatsu Kanal, MD,b and Hitoshi Endou, MDb

aThird Department of Surgery, Nihon University School of Medicine, Tokyo, and bDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine

Address all correspondence and reprint requests to: Hideki Masuda, MD, Third Department of Surgery, Nihon University School of Medicine, 2-11-1. Hikarigaoka, Nerima-ku, Tokyo 179-0072, Japan.

ABSTRACT: The purpose of this study was to examine whether L-type amino acid transporter1 (LAT1), one of the amino acid transporters, is related closely to tumor size in liver metastasis. Rat colon cancer cells (RCN-9) were injected into the capsule of the spleen of 12 male rats (inbred F344/DuCrj). Conversely, four rats received only phosphate-buffered saline (control group 1), and four rats underwent only laparotomy (control group 2). In each rat, the metastatic tumors, areas surrounding tumor nodules, or the livers of the control groups were immunostained with the antibodies to LAT1 C peptide antigen. In control groups 1 and 2, normal hepatocytes did not indicate a staining of LAT1. A total of 90 metastatic nodules were found in 12 livers with metastasis. Of the 90 metastatic nodules, 43 nodules indicated a positive staining of LAT1. Conversely, the remaining 47 metastatic nodules had a negative staining of LAT1. The average size in metastatic nodules in the group with positive staining of LAT1 was 1.6 ± 0.4 mm2, which was significantly higher than that of the group with negative staining of LAT1 (0.6 ± 0.2 mm2; P = .0007). The ratio of the average area of the metastatic nodule against the average largest section of the left lobe of the lateral segment (RML, %) was measured. The RML in the group with positive staining of LAT1 was 1.2 ± 0.3 %, whereas the RML in the group with negative staining of LATI was 0.4 ± 0.1%. A significant difference was noted between the two groups (P = .0004). We concluded that LAT1 plays an important role in tumor cell growth of liver metastatic tumors.

KEY WORDS: liver metastasis, L-type amino acid transporter, tumor growth.