Analysis of mechanism of lymphogenous metastasis using a 4 NQO-induced model of tongue carcinoma in the rat

• Published in: Japanese Journal of Oral and Maxillofacial Surgery Vol. 47; no. 10; pp. 600 - 606
• Main Authors: TANAKA, Azusa, TATEMATSU, Masae, KATO, Mugio, ABE, Atsushi, NAKANISHI, Hayao, KITAMURA, Tabito, TSUKAMOTO, Yoshitaka, KURITA, Kenichi
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Society of Oral and Maxillofacial Surgeons 2001
• Subjects: lymph node metastasis; metastasis model; MMP; tongue carcinoma cell lines
• ISSN: 0021-5163; 2186-1579
• DOI: 10.5794/jjoms.47.600

Lymph node metastasis is the major cause of the poor prognosis of tongue carcinoma. To investigate the mechanism of lymph node metastasis, we developed three lymph node metastasis sublines (RSC 3 E 2, RSC 3 E 2 R, and RSC 3 LM) from 4 NQO-induced tongue squamous cell carcinoma in the rat (RSC 3). LM and E 2 R cells metastasized to the popliteal lymph nodes after injection into the foot pad. Labeling of LM cells with the fluorescence dye Ca-AM revealed fluorescence in the popliteal lymph nodes immediately after injection of the labeled cells. These findings indicate that (1) LM cells have spontaneous metastatic potential, (2) E 2 R cells have experimental metastatic potential, and (3) E 2 cells are nonmetastatic. In vitro and in vivo invasion assays showed that LM cells have higher invasive ability than the other two types of cells. In addition, gelatin zymography revealed that only LM cells carried an activated form of matrix metalloproteinase-2 (MMP-2). These results suggest that the high motility and activated form of MMP-2 may be important for intravasation of LM cells into lymphatic vessels in the primary tumor, leading to spontaneous lymph node metastasis. This model could be useful for investigating the mechanism of lymphatic metastasis of tongue carcinoma cells.