Purpose: To establish a seminoma orthotopic model with lymph node metastasis to investigate the factors related to the lymphophilic behavior of seminoma cells.
Materials and methods: Testicular seminoma xenografts were established by the inoculation of small fragments from subcutaneous (s.c.) xenografts that had previously been established in severe combined immunodeficient (SCID) mice with a supraclavicular lymph node metastasis from a human seminoma. Hematologic dissemination of tumor cells was analyzed by polymerase chain reaction (PCR) amplification of the human beta-globin gene. Xenograft messenger RNA levels of metastasis-related genes were examined by reverse transcription (RT)-PCR.
Results: Testicular seminoma xenografts grew in 32/32 (100%) of the inoculated mice, of which 15 mice (47%) developed macroscopic metastasis to the renal hilar lymph node. Circulating tumor cells and tumor cell shedding in the lung and liver were detectable by PCR assay in 25/32 (78%), 32/32 (100%), and 27/32 (84%) mice, respectively, although metastatic foci were not histologically evident in these organs. Increased expression of matrix metalloproteinase-2 (MMP-2), membrane-type 3 matrix metalloproteinase (MT3-MMP) and vascular endothelial growth factor (VEGF), and reduction in expression of plasminogen activator inhibitor-2 (PAI-2) were demonstrated by RT-PCR assay in the testicular xenografts as compared with the s.c. xenografts.
Conclusions: This model mimics the lymphophilic behavior of seminoma and may help in elucidating the molecular mechanism of tumor spread via the lymphatics.