Qualitative and quantitative analyses of human chorionic gonadotropin and its subunits produced by malignant tumors

Hattori, Masahiro; Yoshimoto, Yoshio; Matsukura, Shigeru; Fujita, Takeshi

doi:10.1002/1097-0142(19800715)46:2<355::aid-cncr2820460224>3.0.co;2-u

Cited by 41 publications

(14 citation statements)

References 20 publications

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“…This is in agreement with the findings of Cowley et al (1985). The hCG-like material isolated from serum and urine of patients with bladder cancer has also been shown to consist mainly of free beta subunit, though smaller molecular weight forms have been noted in urine (Hattori et al, 1980;Norman et al, 1985;Rodenburg et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

Expression of beta human chorionic gonadotrophin by non-trophoblastic non-endocrine 'normal' and malignant epithelial cells

Iles

Purkis²,

Whitehead³

et al. 1990

Br J Cancer

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Summary Expression of hCG and its free subunits by non-trophoblastic tumours is well recognised. Previously we reported hCG secretion by normal and malignant bladder epithelial cells in vitro. Here we examined culture medium from 83 different cell lines derived mainly from common epithelial tumours. Thirty-two of the cell lines were found to secrete hCG-like material into their culture media. Partial immunochemical characterisation showed that of these only choriocarcinoma and fetal tissue cell lines produced intact hCG and alpha subunit. The remaining 28 hCG-expressing epithelial cell lines, which are of mucosal origin, only secreted free beta subunit. Expression of free beta hCG by non-trophoblastic nonendocrine cells would appear to be especially characteristic of mucosal epithelia from the genitourinary and oral/respiratory tracts. Furthermore, this phenomenon may be characteristic of epithelium with transitional and/or squamous cell-like properties.Detection of human chorionic gonadotrophin (hCG) in the blood of non-pregnant subjects is most commonly associated with germ cell tumours. In addition, hCG or either of its two subunits can be found in the serum of some patients with non-gonadal epithelial tumours. The highest incidence of the latter is found with islet cell carcinomas (reviewed by Braunstein, 1983). We have previously reported the expression of the free beta subunit of hCG as a common feature of neoplastic and 'normal' bladder epithelial cells in vitro (Iles et al., 1987;. Similarly, Cowley et al. (1985) found that the secretion of free beta-hCG was a common feature of a series of head and neck squamous carcinoma cell lines. Here we report a survey of the in vitro hCG secretion by 83 cell lines, derived in the main from common epithelial tumours: lung, breast, ovarian, colorectal and bladder. The secreted hCG was further subjected to detailed immunochemical characterisation. Materials and methodsCell culture A total of 83 established and finite cell lines were examined. These included 10 testicular germ cell tumours; three choriocarcinomas; 10 bladder cancers; eight 'normal' urothelial lines; 12 oral and genital epidermoid and squamous cell carcinoma (EC and SCC); four 'normal' oral mucosa; eight normal and transformed skin keratinocytes; five colorectal tumours; five lung carcinomas; seven breast carcinomas; and five ovarian (epithelial) tumours. Six control cell lines (three human and three murine) were also examined.

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Section: Discussionmentioning

confidence: 99%

Expression of beta human chorionic gonadotrophin by non-trophoblastic non-endocrine 'normal' and malignant epithelial cells

Iles

Purkis²,

Whitehead³

et al. 1990

Br J Cancer

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“…Several investigations have given evidence for a disparity between the forms of human choriogonadotropin (hCG)' trophoblast (1)(2)(3)(4)(5)(6)(7). The abnormal forms of hCG and their metabolites are of clinical interest as potential molecular markers of the malignant transformation of the trophoblast.…”

Section: Introductionmentioning

confidence: 64%

Carboxyterminal peptide fragments of the beta subunit are urinary products of the metabolism of desialylated human choriogonadotropin.

Amr¹,

Rosa²,

Birken³

et al. 1985

J. Clin. Invest.

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Previous investigations of patients with gestational trophoblastic neoplasia have shown that their urines often contain carboxyterminal peptide (C1TP) fragments of the choriogonadotropin (hCG) ,8-subunit as well as forms of hCG deficient in sialic acid. In order to determine whether 8-CTP fragments are among the urinary products of the peripheral degradation of desialylated hCG (as-hCG), using a continuous infusion technique, we gave highly purified as-hCG to humans. Six healthy subjects were given a loading dose of 0.8 mg of as-hCG followed by an infusion of the same preparation. An overall mean infusion rate of 62.9 gg/min was maintained for 6 h, and the mean serum concentration of as-hCG achieved during the infusion was 72.1 ng/ml. In all six subjects, l-C'TP fragments were the predominant immunoreactive forms of as-hCG in urine obtained during the infusion. In contrast, the urine of subjects infused with hCG has been shown to contain hCG itself, but nil l-CTP fragments or as-hCG. After the as-hCG infusion was stopped, the excretion of the /3-CTP fragments in urine declined rapidly. There were no ,8-ClP fragments detectable in sera obtained during the infusion or in sera incubated with as-hCG at 37°C. After incubation with as-hCG for 4 h, the urine of normal subjects contained small amounts of fl-CTP fragments; however, the apparent proteolytic activity was too low to account for either the quantity of fl-CTP fragments produced during the infusion or the extremely low levels of ashCG in the urine. These data demonstrate the existence in humans of a peripheral metabolic pathway that cleaves fl-CT? fragments from as-hCG and allows their excretion in urine. Thus, the frequent presence of,-CTP fragments in the urines of patients with gestational trophoblastic neoplasia can be accounted for in part by the metabolism of the forms of hCG that bear an altered carbohydrate structure, which are prevalent in this disease.

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“…Some of these forms of the hormone appear to be subunits of hCG (1)(2)(3)(4)(5)(6)(7), and some appear to be fragments, as they exhibit molecular sizes smaller than those of the hCG subunits (1,5,6,(8)(9)(10)(11). When obtained from different sources, hCG itself has been found to have variable biological, physicochemical, and immunological properties; this microheterogeneity seems to be related, in part, to variations in its carbohydrate composition (10,(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

“…Fragments of this type have been observed in the urine of pregnant women (5,6,8,9), in crude commercial preparations of hCG from pregnancy (16), and in the urine of several patients with trophoblastic neoplasms (1) and nontrophoblastic tumors (1,8,11). We have observed that this type of fragment also appears in the urine after infusion of highly purified hCG/B subunit into normal subjects (17) and, therefore, it is a product of the metabolism of hCGI3.…”

Section: Introductionmentioning

confidence: 99%

Characterization of a carboxyterminal peptide fragment of the human choriogonadotropin beta-subunit excreted in the urine of a woman with choriocarcinoma.

Amr¹,

Wehmann²,

Birken³

et al. 1983

J. Clin. Invest.

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A B S T R A C T We have observed low-molecular weight carboxyterminal fragments of the human choriogonadotropin (hCG) a-subunit in the urines of several women with choriocarcinoma, and we have characterized one fragment in detail. Its apparent molecular weight by gel chromatography on Sephadex G-100 was 14,200. The fragment was not adsorbed to concanavalin A-Sepharose, indicating that it lacked the asparagine-linked carbohydrate groups of intact hCG#. It was active in radioimmunoassays (RIA) using antisera either to the hCG# carboxyterminal peptide (CTP) or to the desialylated hCG# CTP (hCG# as-CTP), indicating the presence of not only the hCG# carboxyterminus but also desialylated O-serine-linked carbohydrate side chains on the fragment. It lacked luteinizing hormone/choriogonadotropin radioreceptor activity and hCG# conformational immunoreactivity (SB6 RIA). On Sephadex G-100 gel chromatography, the elution profiles of this fragment and the hCG# as-CTP(115-145) prepared by trypsin digestion of ashCG were essentially indistinguishable (apparent molecular weights 14,200 and 14,000, respectively). The immunological characteristics of the fragment in both hCG# CTP and hCG# as-CTP RIA were indistinguishable from those of the hCG,6 as-CTP(115-145) glycopeptide. Carboxyterminal fragments of hCG# were evident in urine specimens obtained from 10 of 11 patients with choriocarcinoma but not in those ob-

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Qualitative and quantitative analyses of human chorionic gonadotropin and its subunits produced by malignant tumors

Cited by 41 publications

References 20 publications

Expression of beta human chorionic gonadotrophin by non-trophoblastic non-endocrine 'normal' and malignant epithelial cells

Expression of beta human chorionic gonadotrophin by non-trophoblastic non-endocrine 'normal' and malignant epithelial cells

Carboxyterminal peptide fragments of the beta subunit are urinary products of the metabolism of desialylated human choriogonadotropin.

Characterization of a carboxyterminal peptide fragment of the human choriogonadotropin beta-subunit excreted in the urine of a woman with choriocarcinoma.

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