Alveolar epithelial cells express and secrete parathyroid hormone-related protein.

Hastings, Randolph H.; Duong, Haison; Burton, Douglas W.; Deftos, Leonard J.

doi:10.1165/ajrcmb.11.6.7946399

Cited by 36 publications

(24 citation statements)

References 24 publications

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“…von Kossa's stain, ×200 lial cells. [3,9,14,18], although the physiological functions in normal lung tissues have yet to be determined. In the present study, it was demonstrated by the immunohistochemistry, the RT-PCR method, and IRMA using culture supernatants that IP tumor cells produce PTHrP.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a transplantable tumor line (IP) derived from rat pulmonary carcinoma, developing humoral hypercalcemia of malignancy in IP-bearing rats

et al. 2001

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A transplantable tumor line (IP) was established in syngeneic rats from a spontaneous pulmonary carcinoma found in a male F344 rat aged 25 months. A tissue fragment of IP grew into a nodule, 2-3 cm in diameter, 2-3 weeks after implant, and IP has been serially passed through 26 generations. Lined by cuboidal or columnar epithelial cells, the primary tumor consisted of completely alveolar architecture. However, IP tumors developed various growth patterns such as glandular, acinar, trabecular, cord, and solid, and consisting of epithelial cells showing cellular atypia. Ultrastructurally, neoplastic cells had microvilli, basement membranes, and desmosomes, and occasional cells possessed dense cytoplasmic granules. Interestingly, it was shown by the immunohistochemistry, the RT-PCR method, and immunoradiometric assay that IP tumor cells produce parathyroid hormone-related protein (PTHrP). During a 3-week observation period after implant, IP-bearing rats showed severe emaciation, hypercalcemia, and hypophosphatemia, as well as an increase in osteoclastic areas and a decrease in shaft thickness of the femurs. These were considered to be due to a marked elevation of plasma PTHrP levels. Furthermore, IP-bearing rats developed calcification in various organs including the kidneys, lungs, and heart. These findings in IP-bearing rats were similar to those of humoral hypercalcemia of malignancy (HHM) reported in human cancer patients. PTHrP plays a central role in the development of HHM, but the mechanisms of HHM remain poorly understood. IP may become a useful model for studying the pathogenesis of HHM and the pathophysiological role of PTHrP.

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Section: Discussionmentioning

confidence: 99%

Establishment of a transplantable tumor line (IP) derived from rat pulmonary carcinoma, developing humoral hypercalcemia of malignancy in IP-bearing rats

et al. 2001

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“…Thus amniotic fluid PTHrP could stimulate epithelial growth and differentiation (Kaiser et al 1994) and may assist in the maturation of these tissues and organs. During fetal lung development, PTHrP is predominantly expressed in bronchial epithelia and alveolar type II cells, whereas its receptor is found in the subepithelial mesenchyme (Hastings et al 1994, Rubin et al 1994. PTHrP-deficient mice were found to have lung hypoplasia, arrested canalicular development and impaired epithelial cytodifferentiation (Rubin et al 1997).…”

Section: Discussionmentioning

confidence: 99%

Parathyroid hormone-related protein(1-34) in gestational fluids and release from human gestational tissues

Farrugia¹,

Ho²,

Rice³

et al. 2000

Journal of Endocrinology

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Parathyroid hormone-related protein (PTHrP) is present in fetal and gestational tissues, in which its proposed roles include stimulation of epithelial growth and differentiation, vasodilatation of the uteroplacental vasculature, relaxation of uterine muscle and stimulation of placental calcium transport. The aim of this study was to determine whether the release of PTHrP from gestational tissue explants was tissue specific. In addition, PTHrP concentrations were measured in maternal plasma, umbilical artery and vein plasma, and amniotic fluid from term, uncomplicated pregnancies before the onset of labour. PTHrP was detected in low concentrations in the mother, fetus and placental tissue. Amniotic fluid had ten times the PTHrP concentration compared with that in the maternal or fetal circulations. Using late pregnant human gestational tissues in an in vitro explant system, we found that amnion over placenta, choriodecidua, reflected amnion, and placenta released PTHrP into culture medium in progressively greater amounts over 24 h (P<0·05). This release was not associated with a loss of cell membrane integrity, as indicated by measurement of the intracellular enzyme, lactate dehydrogenase, in the incubation media. After 24 h incubation, the fetal membranes released significantly (P<0·05) greater amounts of PTHrP than did the placenta (placenta 3·7 0·5 pmol PTHrP/g protein). Amnion over placenta released significantly more PTHrP (139·3 43·1 pmol PTHrP/g protein) than did reflected amnion (29·0 8·3 pmol PTHrP/g protein) (P<0·05). This study unequivocally demonstrated that human gestational tissues release PTHrP and it was concluded that the main contributors to PTHrP in amniotic fluid were the human fetal membranes, particularly amnion over placenta. Fetal membrane-derived and amniotic fluid PTHrP are proposed to have stimulatory effects on epithelial growth and differentiation in fetal lung, gut, skin and hair follicles and paracrine effects on placental vascular tone and calcium transport.

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“…Regulation of PTHrP release by PKC has been reported in the NCI-H727 nonsmall lung cancer cell line, alveolar epithelial cells, and human osteosarcoma cell line [121][122][123]. In some cell systems, PKC participates in activation of MEK/ERK cascade [124,125].…”

Section: Regulation By Pkc/mek Pathwaymentioning

confidence: 99%

Calcium-sensing receptor in cancer: good cop or bad cop?

Chakravarti

Dwivedi

Mithal

et al. 2008

Endocr

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The extracellular calcium-sensing receptor (CaR) is a versatile 'sensor' for di- and polycationic molecules in the body. CaR plays a key role in the defense against hypercalcemia by "sensing" extracellular calcium levels in the parathyroid and kidney, the key organs maintaining systemic calcium homeostasis. Although mutation of CaR gene has so far not been associated with any malignancy, aberrant functions of CaR have implications in malignant progression. One situation is loss of CaR expression, resulting in loss of growth suppressing effects of elevated extracellular Ca(2+) by CaR, reported in parathyroid adenoma and in colon carcinoma. Another situation is activation of CaR, resulting in increased production of parathyroid hormone-related peptide (PTHrP), a primary causal factor in hypercalcemia of malignancy and a contributor to metastatic processes involving bone. CaR signaling and effects have been studied in several cancers including ovarian cancers, gastrinomas, and gliomas in addition to comparatively detailed studies in breast, prostate, and colon cancers. Studies on H-500 rat Leydig cells, a xenotransplantable model of humoral hypercalcemia of malignancy has shed much light on the mechanisms of CaR-induced cancer cell growth and survival. Pharmacological agonists and antagonists of CaR hold therapeutic promise depending on whether activation of CaR is required such as in case of colon cancer or inactivating the receptor is required as in the case of breast- and prostate tumors.

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Alveolar epithelial cells express and secrete parathyroid hormone-related protein.

Cited by 36 publications

References 24 publications

Establishment of a transplantable tumor line (IP) derived from rat pulmonary carcinoma, developing humoral hypercalcemia of malignancy in IP-bearing rats

Establishment of a transplantable tumor line (IP) derived from rat pulmonary carcinoma, developing humoral hypercalcemia of malignancy in IP-bearing rats

Parathyroid hormone-related protein(1-34) in gestational fluids and release from human gestational tissues

Calcium-sensing receptor in cancer: good cop or bad cop?

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