A human seminoma xenograft model with regional lymph node metastasis

Purpose: To establish a seminoma orthotopic model with lymph node metastasi s to investigate the factors related to the lymphophilic behavior of semino ma cells. Materials and Methods: Testicular seminoma xenografts were established by t he inoculation of small fragments from subcutaneous (s.c.) xenografts that had previously been established in severe combined immunodeficient (SCID) m ice with a supraclavicular lymph node metastasis from a human seminoma. Hem atologic dissemination of tumor cells was analyzed by polymerase chain reac tion (PCR) amplification of the human beta-globin gene. Xenograft messenger RNA levels of metastasis-related genes were examined by reverse transcript ion (RT)-PCR. Results: Testicular seminoma xenografts grew in 32/32 (100%) of the inocula ted mice, of which 15 mice (47%) developed macroscopic metastasis to the re nal hilar lymph node. Circulating tumor cells and tumor cell shedding in th e 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 hist ologically evident in these organs. Increased expression of matrix metallop roteinase-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 ma y help in elucidating the molecular mechanism of tumor spread via the lymph atics.