SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular cancer.
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.
Nagahara
Akira
A
Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka 565-0871, Japan.
Nakayama
Masashi
M
Oka
Daizo
D
Tsuchiya
Mutsumi
M
Kawashima
Atsunari
A
Mukai
Masatoshi
M
Nakai
Yasutomo
Y
Takayama
Hitoshi
H
Nishimura
Kazuo
K
Jo
Yoshimasa
Y
Nagai
Atsushi
A
Okuyama
Akihiko
A
Nonomura
Norio
N
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019394:Ki-67 Antigen / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009373:Neoplasms, Germ Cell and Embryonal / Q000378:metabolism / Q000473:pathology*; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D058258:Serpin E2; D013736:Testicular Neoplasms / Q000378:metabolism / Q000473:pathology*; D033921:Vesicular Transport Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D019394:Ki-67 Antigen; C119248:LYVE1 protein, human; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C545486:SERPINE2 protein, human; D058258:Serpin E2; D033921:Vesicular Transport Proteins