Role of assays for parathyroid-hormone-related protein in investigation of hypercalcaemia

Ratcliffe, W. A.; Hutchesson, A. C. J.; Bundred, Nigel; Ratcliffe, John G.

doi:10.1016/0140-6736(92)90220-w

Cited by 131 publications

(82 citation statements)

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“…(Ellison et al, 1975;Strewler et al, 1983;Sato et al, 1987;Merryman et al, 1989;Miyake et al, 1991;De Miguel and Esbrit, 1992;Ichinose et al, 1993;Tabuenca et al, 1995;Birch et al, 1995). Although immunohistochemical and molecular analyses clearly demonstrate that the majority of breast cancer cells express PTHrP in primary tumours and metastatic sites and, in particular, in bone metastasis (Southby et al, 1990;Powell et al, 1991;Bundred et al, 1992;Vargus et al, 1992;Bouizar et al, 1993;Kohno et al, 1994a,b), only a little experimental data have been published so far concerning PTHrP secretion from established breast cancer cell lines (Tabuenca et al, 1995;Birch et al, 1995 (Martin, 1988;Mundy, 1990). Recently, newly developed agents, such as bisphosphonate, which decrease the osteolytic activity of osteoclasts, have been used clinically for malignancy-associated hypercalcaemia caused by multiple osteolytic metastases or a high blood level of PTHrP secreted by malignancies (Body et al, 1986(Body et al, , 1989Dumon et al, 1991).…”

Section: Microcalcifications In the Transplanted Tumoursmentioning

confidence: 99%

“…This protein was originally isolated from human malignant tumours associated with humoral hypercalcaemia. A number of clinical studies indicate that PTHrP is the main cause of HHM (Burtis et al, 1990;Grill et al, 1991;Ratcliffe et al, 1992). In other words, tumour-derived PTHrP acts as a circulating hormone like parathyroid hormone and induces hypercalcaemia.…”

mentioning

confidence: 99%

“…In other words, tumour-derived PTHrP acts as a circulating hormone like parathyroid hormone and induces hypercalcaemia. Recently, a series of studies has indicated that PTHrP is commonly expressed in breast cancer and that a higher expression of PTHrP may induce bone metastasis (Southby et al, 1990;Powell et al, 1991;Bundred et al, 1992;Vargus et al, 1992;Bouizar et al, 1993;Kohno et al, 1994a;Kohno et al, 1994b). It is conceivable that the PTHrP secreted by breast cancer cells, which exist in bone marrow, may act as a paracrine effector on osteoclasts, resulting in osteolytic involvement.…”

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confidence: 99%

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A new human breast cancer cell line, KPL-3C, secretes parathyroid hormone-related protein and produces tumours associated with microcalcifications in nude mice

Kurebayashi

Kurosumi²,

Sonoo³

1996

Br J Cancer

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Summary Parathyroid hormone-related protein (PTHrP) is the main cause of humoral hypercalcaemia of malignancy (HHM). We recently established a new human breast cancer cell line, designated KPL-3C, from the malignant effusion of a breast cancer patient with HHM. Morphological, cytogenetic and immunohistochemical analyses indicated that the cell line is derived from human breast cancer. The KPL-3C cells stably secrete immunoreactive PTHrP measured by a two-site immunoradiometric assay, possess both oestrogen and progesterone receptors and are tumorigenic in female nude mice. The addition of phorbol-12-myristate-13-acetate to the medium significantly increased PTHrP secretion from the cells. In contrast, hydrocortisone, medroxyprogesterone acetate and 22-oxacalcitriol decreased PTHrP secretion in a dose-dependent manner. Unexpectedly, a number of microcalcifications were observed in the transplanted tumours. Radiographical examination indicated that the microcalcifications in the tumours are very similar to those commonly observed in human breast cancer. These findings suggest that this KPL-3C cell line may be useful for studying the regulatory mechanisms of PTHrP secretion and the mechanisms that lead to the deposition of microcalcifications in breast cancer.Keywords: breast cancer; hypercalcaemia; cell line; parathyroid hormone-related protein; microcalcification Parathyroid hormone-related protein (PTHrP) is a recently discovered protein sharing strong homology with parathyroid hormone in the N-terminal amino acid sequence as well as biological activity (Suva et al., 1987;Mangin et al., 1988). This protein was originally isolated from human malignant tumours associated with humoral hypercalcaemia. A number of clinical studies indicate that PTHrP is the main cause of HHM (Burtis et al., 1990;Grill et al., 1991;Ratcliffe et al., 1992). In other words, tumour-derived PTHrP acts as a circulating hormone like parathyroid hormone and induces hypercalcaemia. Recently, a series of studies has indicated that PTHrP is commonly expressed in breast cancer and that a higher expression of PTHrP may induce bone metastasis (Southby et al., 1990;Powell et al., 1991;Bundred et al., 1992;Vargus et al., 1992;Bouizar et al., 1993;Kohno et al., 1994a;Kohno et al., 1994b). It is conceivable that the PTHrP secreted by breast cancer cells, which exist in bone marrow, may act as a paracrine effector on osteoclasts, resulting in osteolytic involvement. These findings suggest that the PTHrP secreted by malignant tumours may act as a hormone or paracrine effector in different pathological situations.Microcalcifications are commonly observed in breast cancer tissues (Snyder and Rosen, 1971 al., 1993).We recently established a new human breast cancer cell line, designated KPL-3C, which is derived from the malignant effusion of a breast cancer patient with HHM. Preliminary characterisation of this cell line and the inhibitory effect of steroid hormones on PTHrP secretion are described in the present paper. Materials and methodsThe clinical co...

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Section: Microcalcifications In the Transplanted Tumoursmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A new human breast cancer cell line, KPL-3C, secretes parathyroid hormone-related protein and produces tumours associated with microcalcifications in nude mice

Kurebayashi

Kurosumi²,

Sonoo³

1996

Br J Cancer

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“…PTHrP secreted by malignant cells has been proved to be the main cause of humoral hypercalcaemia associated with malignancy (Burtis et al, 1990; Grill et al, 1991;Ratcliffe et al, 1992). In this situation, PTHrP acts on kidney and bone as a circulating hormone like parathyroid hormone and subsequently induces hypercalcaemia.…”

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confidence: 99%

Parathyroid hormone-related protein secretion is inhibited by oestradiol and stimulated by antioestrogens in KPL-3C human breast cancer cells

Kurebayashi

Sonoo²

1997

Br J Cancer

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Summary We recently established a human breast cancer cell line, KPL-3C, from a breast cancer patient with humoral hypercalcaemia. This cell line possesses oestrogen receptor (ER) and secretes parathyroid hormone-related protein (PTHrP) into medium. To investigate the effects of oestrogen and antioestrogens on PTHrP secretion, KPL-3C cells were cultured for 48 h in an oestrogen-eliminated medium with 17,B-oestradiol (E2), tamoxifen (TAM) and/or a pure antioestrogen, IC1182,780 (ICI), and PTHrP secretion was measured using an immunoradiometric assay. The effects of these agents on cell cycle progression were also studied using flow cytometry. E2 (1-100 nM) significantly inhibited PTHrP secretion, whereas both TAM (0.1-10 gM) and ICI (1-100 nM) significantly stimulated it. These effects were completely blocked by the simultaneous addition of 1 nM E2 to the medium. At the same time, E2 significantly increased the percentage of cells during the S and G/M phases, whereas both antioestrogens significantly increased the percentage of cells during the GO/G1 phase. Again, these cytostatic effects were completely reversed by the addition of E2. These findings indicate that antioestrogens inhibit the growth of ERpositive breast cancer cells but may stimulate PTHrP secretion and that these effects may be mediated by ER.

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“…This is particularly true for solid tumours (Ratcliffe et al, 1992). PTHrP has all the known biological effects of PTH and produces them by acting on a common PTH/PTHrP receptor (Martin, 1990).…”

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confidence: 99%

Parathyroid hormone related protein

Heath

1993

Clinical Endocrinology

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Role of assays for parathyroid-hormone-related protein in investigation of hypercalcaemia

Cited by 131 publications

References 22 publications

A new human breast cancer cell line, KPL-3C, secretes parathyroid hormone-related protein and produces tumours associated with microcalcifications in nude mice

A new human breast cancer cell line, KPL-3C, secretes parathyroid hormone-related protein and produces tumours associated with microcalcifications in nude mice

Parathyroid hormone-related protein secretion is inhibited by oestradiol and stimulated by antioestrogens in KPL-3C human breast cancer cells

Parathyroid hormone related protein

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