SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular cancer

• Published in: Biochemical and biophysical research communications Vol. 391; no. 4; pp. 1641 - 1646
• Main Authors: Nagahara, Akira, Nakayama, Masashi, Oka, Daizo, Tsuchiya, Mutsumi, Kawashima, Atsunari, Mukai, Masatoshi, Nakai, Yasutomo, Takayama, Hitoshi, Nishimura, Kazuo, Jo, Yoshimasa, Nagai, Atsushi, Okuyama, Akihiko, Nonomura, Norio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.01.2010
• Subjects: 60 APPLIED LIFE SCIENCES; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Animals; CELL CULTURES; GENES; GERM CELLS; IN VITRO; Ki-67 Antigen - metabolism; LUNGS; LYMPH NODES; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphatic Metastasis; Male; METASTASES; Metastasis; MICE; Neoplasm Transplantation; NEOPLASMS; Neoplasms, Germ Cell and Embryonal - metabolism; Neoplasms, Germ Cell and Embryonal - pathology; PROMOTERS; Protease Nexins; PROTEINS; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Secreted protein; Serpin E2; SERPINE2; TESTES; Testicular germ cell tumor; Testicular Neoplasms - metabolism; Testicular Neoplasms - pathology; Vesicular Transport Proteins - metabolism; Xenograft; Secreted protein; Xenograft; TGCT; SERPINE2; CM; Metastasis; Testicular germ cell tumor
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2009.12.105

Testicular germ cell tumors (TGCTs) commonly metastasize to the lymph node or lung. However, it remains unclear which genes are associated with TGCT metastasis. The aim of this study was to identify gene(s) that promoted human TGCT metastasis. We intraperitoneally administered conditioned medium (CM) from JKT-1, a cell-line from a human testicular seminoma, or JKT-HM, a JKT-1 cell sub-line with high metastatic potential, into mice with JKT-1 xenografts. Administration of CM from JKT-HM significantly promoted lymph node metastasis. A cDNA microarray analysis showed that JKT-HM cells highly expressed the Serpine peptidase inhibitor, clade E, member 2 (SERPINE2), which encodes a secreted protein. Administration of CM from SERPINE2-silenced JKT-HM cells inhibited lymph node metastasis in the xenograft model, compared with administration of CM from JKT-HM cells. There was no significant difference in xenograft volume. Moreover, administration of CM from SERPINE2-over-expressing JKT-1 was likely to promote lymph node metastasis in the xenograft model. There was no difference in the in vitro proliferation or migration of JKT-1 cells cultured with CM from JKT-HM cells, compared to that with CM from JKT-1. There was no promotion of proliferation or lymphangiogenesis in the xenografts, as measured by Ki-67 and LYVE-1 immunohistochemistry, respectively. Although we could not clarify how SERPINE2 promoted lymph node metastasis, it may be a promoter in the development of lymph node metastasis in the human seminoma cells in a mouse xenograft model.