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

Shingo Hatakeyama, Chikara Ohyama, Shingo Minagawa, Takamitsu Inoue, Hideaki Kakinuma, Atsushi Kyan, Yoiehi Arai, Tomoaki Suga, Jun Nakayama, Tetsuro Kato, Tomonori Habuchi, Michiko N. Fukuda

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

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 immunohistochemistry using antitrophinin antibody. This screening identified trophinin-positive specimens with the frequencies 39 of 91 (43%) in stage I, 14 of 24 (58%) in stage II, 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-β 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 trophininexpressing JKT-1-Tro cells are more invasive than JKT-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 (n = 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.

Original languageEnglish
Pages (from-to)4257-4262
Number of pages6
JournalCancer Research
Volume64
Issue number12
DOIs
Publication statusPublished - 2004 Jun 15
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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