Functional correlation of trophinin expression with the malignancy of testicular germ cell tumor

被引:29
作者
Hatakeyama, S
Ohyama, C
Minagawa, S
Inoue, T
Kakinuma, H
Kyan, A
Arai, Y
Suga, T
Nakayama, J
Kato, T
Habuchi, T
Fukuda, MN
机构
[1] Burnham Inst, Glycobiol Program, Ctr Canc Res, La Jolla, CA 92037 USA
[2] Akita Univ, Sch Med, Dept Urol, Akita, Japan
[3] Tohoku Univ, Sch Med, Dept Urol, Sendai, Miyagi, Japan
[4] Shinshu Univ, Sch Med, Dept Internal Med, Matsumoto, Nagano, Japan
[5] Shinshu Univ, Grad Sch Med, Dept Pathol, Matsumoto, Nagano, Japan
关键词
D O I
10.1158/0008-5472.CAN-04-0732
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Trophinin is a membrane protein that is potentially involved in human embryo implantation by mediating homophillic cell adhesion between trophoblastic cells and endometrial cells. Trophinin expression by maternal cells may be induced by the embryo that secretes human chorionic gonadotropin (hCG). Because the process of tumor metastasis resembles that of trophoblast invasion and proliferation during embryo implantation, we hypothesized that testicular cancers that synthesize hCG express trophinin thus becoming aggressive trophoblast-like cells. We screened paraffin-embedded orchiectomy specimens of 158 patients with testicular germ cell tumor by immumohistochemistry using antitrophinin antibody. This screening identified trophinin-positive specimens with the frequencies 39 of 91 (43%) in stage 1, 14 of 24 (58%) in stage 11, and 41 of 43 (95%) in stage III (P < 0.001). Thus, trophinin expression positively correlates with clinical stage. Remarkably, trophinin was found in all of the cases (33 of 33) with lung metastasis. The levels of serum hCG-beta were significantly higher in the patients with trophinin-positive tumors than those with trophinin-negative tumors (P = 0.004). To determine whether trophinin promotes aggressiveness of the cell, trophinin-negative human seminona cell line JKT-1 was stably transfected with a mammalian expression vector containing trophinin cDNA. In vitro assays revealed that trophinin-expressing JKT-1-Tro cells are more invasive than XT-1-mock cells, whereas there are no differences between JKT-1-Tro and JKT-1-mock in their proliferation activity. Upon orthotopic inoculation to athymic nude mice, JKT-1-Tro cells exhibited i.p. metastases in all of the mice In = 5), whereas JKT-1-mock produced no metastases (n = 5). These results suggest strongly that trophinin enhances invasiveness of the cells and promotes metastasis of testicular germ cell tumor.
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页码:4257 / 4262
页数:6
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