Artificial lymphogenous metastatic model using orthotopic implantation of human lung cancer.

Abstract

We established a new, patientlike orthotopic model of lung cancer metastasis with human non-small cell lung cancer cell lines. In this report, we describe the progressive stages of development of lymphogenous mediastinal metastasis in the Ma44-3 cell line from day 3 to day 15 after implantation in severe combined immunodeficiency mice and the process of lymphogenous metastasis. All mice killed after day 12 had perivascular and peribronchial tumor growth. Micrometastasis to the mediastinum was first observed on day 5. On days 5 through 9, 10 of 13 mice had metastasis to the mediastinum, and all mice had one by day 12. When perivascular and peribronchial tumor growth was present by day 5, metastasis to the mediastinum developed in all mice. This study demonstrates the lymphogenous spread of human lung cancer in severe combined immunodeficiency mouse using an orthotopic implantation model. Our model was thought to be an artificial lymphogenous metastasis model, owing to forced tumor inoculation into lymphatic vessels.