Effect of a matrix metalloproteinase inhibitor on a lymph node metastatic model of gastric cancer cells passaged by orthotopic implantation

Lymph node metastasis is the most frequent type of tumor recurrence and is known to be one reason for the poor prognosis in patients with digestive cancer. However, the mechanisms of lymph node metastasis are not clearly understood and a metastatic model will be useful for elucidating factors associated with lymph node metastases. In this study, we investigated the effect of R-94138, a matrix metalloproteinase (MMP) inhibitor, on the lymphnodal metastatic ability of gastric cancer cells using an in vivo orthotopic implantation model in nude mice. Injection of a gastric cancer cell line, MKN-45, into the gastric wall resulted in lymph node metastasis 8 weeks after inoculation. The number of lymph node metastases and the amount of body weight loss significantly decreased by intraperitoneal administration of R-94138. Histologically, lymphatic invasion of cancer cells was found in primary gastric tumors of control mice with lymph node metastasis. However, no lymphatic invasion was observed in the gastric wall of R-94138-treated mice without lymph node metastasis. These findings suggested that the MMP inhibitor, R-94138, could be used in adjunctive therapy for lymph node metastasis in gastric carcinoma.