Regulation of secretion of PTHrP by Ca2+-sensing receptor in human astrocytes, astrocytomas, and meningiomas

被引:56
作者
Chattopadhyay, N
Evliyaoglu, C
Heese, O
Carroll, R
Sanders, J
Black, P
Brown, EM
机构
[1] Harvard Univ, Brigham & Womens Hosp, Div Endocrine Hypertens, Boston, MA 02115 USA
[2] Harvard Univ, Brigham & Womens Hosp, Dept Med, Membrane Biol Program, Boston, MA 02115 USA
[3] Harvard Univ, Brigham & Womens Hosp, Dept Surg, Div Neurol Surg, Boston, MA 02115 USA
[4] Univ Kocaeli, Sch Med, Dept Neurosurg, Kocaeli, Turkey
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2000年 / 279卷 / 03期
关键词
brain tumor; glioma; proliferation; humoral hypercalcemia of malignancy;
D O I
10.1152/ajpcell.2000.279.3.C691
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Parathyroid hormone-related protein (PTHrP) is the major mediator of the humoral hypercalcemia of malignancy and of malignant osteolysis associated with skeletal metastases of common epithelial cancers. PTHrP secretion is regulated by the extracellular calcium concentration ([Ca2+](o)) in several types of normal and malignant cells. Because the [Ca2+](o)-sensing receptor (CaR) is a key mediator of [Ca2+](o)-regulated hormone secretion [e.g., of parathyroid hormone (PTH) by parathyroid chief cells], we investigated the expression of the CaR and PTHrP in normal and neoplastic glial cells and studied the effects of [Ca2+](o) on PTHrP secretion. Our results show that primary embryonic human astrocytes (HPA) express CaR mRNA and protein as detected by RT-PCR and Western analysis, respectively. Furthermore, astrocytomas and meningiomas also express the CaR at similar levels as assessed by RT-PCR and Northern and Western blot analyses. HPA and astrocytomas express transcripts encoding all three known isoforms of PTHrP [PTHrP(139), PTHrP(141), and PTHrP(173), comprising 139, 141, and 173 predicted amino acid residues, respectively] as assessed by RT-PCR, whereas meningiomas express only the first two of these. Finally, elevated levels of [Ca2+](o) and other polycationic CaR agonists dose dependently stimulate PTHrP secretion from HPA, astrocytomas, and meningiomas, although both basal and high [Ca2+](o)-stimulated rates of PTHrP secretion are similar to 2.5-fold higher in HPA than in the glial tumors studied here. Therefore, our results show that HPA, astrocytomas, and meningiomas express both the CaR and PTHrP and that CaR agonists stimulate PTHrP secretion.
引用
收藏
页码:C691 / C699
页数:9
相关论文
共 51 条
[21]  
2-M
[22]   IDENTIFICATION AND CHARACTERIZATION OF PARATHYROID-HORMONE PARATHYROID HORMONE-RELATED PEPTIDE RECEPTOR IN CULTURED ASTROCYTES [J].
HASHIMOTO, H ;
AINO, H ;
OGAWA, N ;
NAGATA, S ;
BABA, A .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 200 (02) :1042-1048
[23]   Parathyroid hormone-related protein, an autocrine growth inhibitor of alveolar type II cells [J].
Hastings, RH ;
SummersTorres, D ;
Yaszay, B ;
LeSueur, J ;
Burton, DW ;
Deftos, LJ .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1997, 272 (03) :L394-L399
[24]   EPIDERMAL GROWTH FACTOR-STIMULATED PARATHYROID HORMONE-RELATED PROTEIN EXPRESSION INVOLVES INCREASED GENE-TRANSCRIPTION AND MESSENGER-RNA STABILITY [J].
HEATH, JK ;
SOUTHBY, J ;
FUKUMOTO, S ;
OKEEFFE, LM ;
MARTIN, TJ ;
GILLESPIE, MT .
BIOCHEMICAL JOURNAL, 1995, 307 :159-167
[25]  
HENDERSON J, 1991, CANCER RES, V51, P6521
[26]  
Iezzoni JC, 1998, MODERN PATHOL, V11, P265
[27]  
IKEDA K, 1989, J BIOL CHEM, V264, P15743
[28]   Reduced immunostaining for the extracellular Ca sensing receptor in primary and uremic secondary hyperparathyroidism [J].
Kifor, O ;
Moore, FD ;
Wang, P ;
Goldstein, M ;
Vassilev, P ;
Kifor, I ;
Hebert, SC ;
Brown, EM .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1996, 81 (04) :1598-1606
[29]   Expression and action of parathyroid hormone-related peptide in human cervical epithelial cells [J].
Kremer, R ;
Woodworth, CD ;
Goltzman, D .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1996, 271 (01) :C164-C171
[30]  
Kronenberg HM, 1998, RECENT PROG HORM RES, V53, P283