title: Functional correlation of trophinin expression with the malignancy of testicular germ cell tumor.
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-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 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.
authors.affiliation: Department of Urology, Akita University School of Medicine, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohyama
authors.forename: Shingo
authors.initials: S
authors.lastname: Minagawa
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Inoue
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kakinuma
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kyan
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Suga
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kato
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.forename: Michiko N
authors.initials: MN
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000096:biosynthesis / Q000097:blood; D004730:Endothelium, Vascular / Q000166:cytology; D018237:Germinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008168:Lung / Q000098:blood supply; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014162:Transfection
chemical_list: D015815:Cell Adhesion Molecules; D018997:Chorionic Gonadotropin, beta Subunit, Human; C093649:TRO protein, human