Skip to main content
SpringerLink
Log in

Parathyroid Hormone-Related Peptide and Malignancy

  • Chapter
Bone Metastasis

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

  • 717 Accesses

Abstract

Parathyroid hormone-related peptide (PTHrP) was originally isolated as a causal factor for hypercalcemia of malignancy (HM), one of the most frequent paraneoplastic syndromes. The association of hypercalcemia with malignancy was originally assumed to be the result of tumor invasion of bone with resultant osteolysis (1,2), but subsequent studies demonstrated an association of hypercalcemia with cancer, even when the tumor had not metastasized to bone. In a careful clinical analysis of a case of renal cell carcinoma with metastases, it was noted that hypercalcemia was associated with hypophosphatemia (3). It was therefore postulated, because lysis of bone should liberate both calcium and phosphate, that the tumor was producing a factor that was both hypercalcemic and phosphaturic, analogous to parathyroid hormone (PTH) (3). The concept arose that tumors might “ectopically” produce PTH, which is normally expressed only in the parathyroid gland. The term “pseudohypoparathyroidism” was therefore employed to describe a syndrome in which cancers had not metastasized to bone, but were associated with hypercalcemia and other PTH-like biochemical abnormalities (4). Certain biochemical alterations were, however, found to differ in primary hyperparathyroidism and “pseudohyperparathyroidism,” including a higher level of serum calcium in the latter and a tendency in the latter toward an alkalosis rather than an acidosis. The development of sensitive bioassays for PTH-like bioactivity confirmed the presence of PTH-like material in the tumors and serum of patients with pseudohyperparathyroidism (5). Although analyses of tumors for PTH-protein (6) and mRNA-encoding PTH (7) failed to detect PTH in this syndrome, a PTH-like substance was subsequently isolated and cloned from several tumors (8–10). This material was referred to initially as both PTH-like peptide and PTH-related peptide and is now known by the term “PTH-related peptide” (PTHrP).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Zondek H, Petrow H, Siebert W. Die bedeutung der calcium-bestimmung in blute fur die diagnose der nierrenin-siffizientz. Z Clin Med 1923; 99:129–132.

    Google Scholar 

  2. Gutman AB, Tyson TL, Gutman EB. Serum calcium, inorganic phosphorus and phosphatase activity in hyperparathyroidism, Paget’s disease, multiple myeloma and neoplastic disease of the bones. Arch Intern Med 1936; 57:379–413.

    CAS  Google Scholar 

  3. Albright F. Case records of the Massachusetts General Hospital (case 27461). N Engl J Med 1941; 225:789–791.

    Article  Google Scholar 

  4. Lafferty FW. Pseudohyperparathyroidism. Medicine 1966; 45:247–260.

    Article  PubMed  CAS  Google Scholar 

  5. Goltzman D, Stewart AF, Broadus AE. Malignancy associated hypercalcemia: evaluation with cytochemical bioassay for parathyroid hormone. J Clin Endocrinol Metab 1981; 53:899–904.

    PubMed  CAS  Google Scholar 

  6. Sherwood LM, O’Riordan JLH, Aurbach GD, Potts JT. Production of parathyroid hormone by nonparathyroid tumors. J Clin Endocrinol Metab 1967; 27:140–144.

    PubMed  CAS  Google Scholar 

  7. Simpson EL, Mundy GR, D’Souza SM, Ibbotson KJ, Bockman MD, Jacobs JW. Absence of parathyroid hormone messenger RNA in non-parathyroid tumors associated with hypercalcemia. N Engl J Med 1983; 309(6):325–330.

    Article  PubMed  CAS  Google Scholar 

  8. Suva LJ, Winslow GA, Wettenhall RE, Hammonds RG, Moseley JM, Diefenbach-Jagger H, Rodda CP, et al. A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression. Science 1987; 237(4817):893–896.

    Article  PubMed  CAS  Google Scholar 

  9. Burtis WJ, Wu J, Bunch CM, Wysolmerski TJ, Jusogna KL, Weir EC, et al. Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. J Biol Chem 1987; 262:7151–7156.

    PubMed  CAS  Google Scholar 

  10. Strewler GJ, Stern PH, Jacobs JW, Eveloff J, Klein RF, Leung SC, et al. Parathyroid hormonelike protein from human renal carcinoma cells. Structural and functional homology with parathyroid hormone. J Clin Invest 1987; 80:1803–1807.

    PubMed  CAS  Google Scholar 

  11. Usdin TB, Hoare SR, Wang T, Mezey E, Kowalak JA. TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus. Nat Neurosci 1999; 2(11):941–943.

    Article  PubMed  CAS  Google Scholar 

  12. Goltzman D, Hendy GN, Banville D. Parathyroid hormone-like peptide: molecular characterization and biological properties. Trends Endocrinol Metab 1989; 1:39–44.

    Article  PubMed  CAS  Google Scholar 

  13. Gensure RC, Ponugoti B, Gunes Y, Papasani MR, Lanske B, Bastepe M, et al. Identification and characterization of two PTH-like molecules in zebrafish. Endocrinology 2003; 145:1634–1639.

    Article  PubMed  CAS  Google Scholar 

  14. Southby J, O’Keefe LM, Martin TJ, Gillespie MT. Alternative promoter usage and mRNA splicing pathways for parathyroid hormone-related protein in normal tissues and tumours. Br J Cancer 1995; 72:702–707.

    PubMed  CAS  Google Scholar 

  15. Holt EH, Vasavada RC, Bander NH, Broadus AE, Philbrick WM. Region-specific methylation of the parathyroid hormone-related peptide gene determines its expression in human renal carcinoma cell lines. J Biol Chem 1993; 268:20,639–20,645.

    PubMed  CAS  Google Scholar 

  16. Sidler B, Alpert L, Henderson JE, Deckelbaum R, Amizuka N, Silva JE, et al. Amplification of the parathyroid hormone-related peptide (PTHrP) gene in a colonic carcinoma. J Clin Endocrinol Metab 1996; 81:2841–2847.

    Article  PubMed  CAS  Google Scholar 

  17. Kremer R, Karaplis AC, Henderson JE, Gulliver W, Banville D, Hendy GN, et al. Regulation of parathyroid hormone-like peptide in cultured normal human keratinocytes. J Clin Invest 1991; 87:884–893.

    PubMed  CAS  Google Scholar 

  18. Sebag M, Henderson JE, Goltzman D, Kremer R. Regulation of parathyroid hormone-related peptide production in normal human mammary epithelial cells in vitro. Am J Physiol 1994; 267:C723–C730.

    PubMed  CAS  Google Scholar 

  19. Kakonen SM, Selander KS, Chirgwin JM, Yin JJ, Burns S, Rankin WA, Grubbs BG, et al. Transforming growth factor-beta stimulates parathyroid hormone-related protein and osteolytic metastases via Smad and mitogen-activated protein kinase signaling pathways. J Biol Chem 2002; 277(27):24,571–24,578.

    Article  PubMed  CAS  Google Scholar 

  20. Haq M, Kremer R, Goltzman D, Rabbani SA. A vitamin D analogue (EB1089) inhibits parathyroid hormone-related peptide production and prevents the development of malignancy-associated hypercalcemia in vivo. J Clin Invest 1993; 91:2416–2422.

    PubMed  CAS  Google Scholar 

  21. Pizzi H, Gladu J, Carpio L, Miao D, Goltzman D, Rabbani SA. Androgen regulation of parathyroid hormone-related peptide production in human prostate cancer cells. Endocrinology 2003; 144(3): 858–867.

    Article  PubMed  CAS  Google Scholar 

  22. Cornish J, Callon KE, Lin C, Xiao C, Moseley JM, Reid IR. Stimulation of osteoblast proliferation by C-terminal fragments of parathyroid hormone-related protein. J Bone Miner Res 1999; 14(6):915–922.

    Article  PubMed  CAS  Google Scholar 

  23. Henderson JE, Amizuka N, Warshawsky H, Biasotto D, Lanske BMK, Goltzman D, et al. Nucleolar targeting of PTHrP enhances survival of chondrocytes under conditions that promote cell death by apoptosis. Mol Cell Biol 1995; 15:4064–4075.

    PubMed  CAS  Google Scholar 

  24. Lam MH, Briggs LJ, Hu W, Martin TJ, Gillespie MT, Jans DA. Importin beta recognizes parathyroid hormone-related protein with high affinity and mediates its nuclear import in the absence of importin alpha. J Biol Chem 1999; 274:7391–7380.

    Article  PubMed  CAS  Google Scholar 

  25. Nguyen M, He B, Karaplis A. Nuclear forms of parathyroid hormone-related peptide are translated from non-AUG start sites downstream from the initiator methionine. Endocrinology 2001; 142(2):694–703.

    Article  PubMed  CAS  Google Scholar 

  26. Aarts MM, Rix A, Guo J, Bringhurst R, Henderson JE. The nucleolar targeting signal (NTS) of parathyroid hormone related protein mediates endocytosis and nucleolar translocation. J Bone Miner Res 1999; 14: 1493–1503.

    Article  PubMed  CAS  Google Scholar 

  27. Meerovitch K, Wing S, Goltzman D. Proparathyroid hormone-related protein is associated with the chaperone protein BiP and undergoes proteasome-mediated degradation. J Biol Chem 1998; 273(33):21,025–21,030.

    Article  PubMed  CAS  Google Scholar 

  28. Juppner H, Abou-Samra A-B, Freeman M, Kong XF, Schipani E, Richards J, et al. A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. Science 1991; 254:1024–1026.

    Article  PubMed  CAS  Google Scholar 

  29. Abou-Samra AB, Juppner H, Force T, Freeman MW, Kong XF, Schipani E, et al. Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: A single receptor stimulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular free calcium. Proc Natl Acad Sci USA 1992; 89:2732–2736.

    Article  PubMed  CAS  Google Scholar 

  30. Usdin TB, Gruber C, Bonner TI. Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor. J Biol Chem 1995; 270(26): 15,455–15,458.

    Article  PubMed  CAS  Google Scholar 

  31. Radeff JM, Singh AT, Stern PH. Role of protein kinase A, phospholipase C and phospholipase D in parathyroid hormone receptor regulation of protein kinase Calpha and interleukin-6 in UMR-106 osteoblastic cells. Cell Signal 2004; 16(1):105–114.

    Article  PubMed  CAS  Google Scholar 

  32. Miao D, Tong XK, Chan GK, Panda D, McPherson PS, Goltzman D. Parathyroid hormone-related peptide stimulates osteogenic cell proliferation through protein kinase C activation of the Ras/mitogen-activated protein kinase signaling pathway. J Biol Chem 2001; 276(34):32,204–32,213.

    Article  PubMed  CAS  Google Scholar 

  33. Kalinowski L, Dobrucki LW, Malinski T. Nitric oxide as a second messenger in parathyroid hormone-related protein signaling. J Endocrinol 2001; 170(2):433–440.

    Article  PubMed  CAS  Google Scholar 

  34. Kaiser SM, Laneuville P, Bernier SM, Rhim JS, Kremer R, Goltzman D. Enhanced growth of a human keratinocyte cell line induced by antisense RNA for parathyroid hormone-related peptide. J Biol Chem 1992; 267(19): 13,623–13,628.

    PubMed  CAS  Google Scholar 

  35. VanHouten JN, Dann P, Stewart AF, Watson CJ, Pollak M, Karaplis AC, et al. Mammary-specific deletion of parathyroid hormone-related protein preserves bone mass during lactation. J Clin Invest 2003; 112(9): 1429–1436.

    Article  PubMed  CAS  Google Scholar 

  36. Macica CM, Broadus AE. PTHrP regulates cerebral blood flow and is neuroprotective. Am J Physiol Regul Integr Comp Physiol 2003; 284(4):R1019,1020.

    Google Scholar 

  37. Stuart WD, Maeda S, Khera P, Fagin JA, Clemens TL. Parathyroid hormone-related protein induces G1 phase growth arrest of vascular smooth muscle cells. Am J Physiol Endocrinol Metab 2000; 279(1):E60–E67.

    PubMed  CAS  Google Scholar 

  38. Hastings RH, Quintana RA, Sandoval R, Duey D, Rascon Y, Burton DW, Deftos LJ. Proapoptotic effects of parathyroid hormone-related protein in type II pneumocytes. Am J Respir Cell Mol Biol 2003; 29(6): 733–742.

    Article  PubMed  CAS  Google Scholar 

  39. Aya K, Tanaka H, Ichinose Y, Kobayashi M, Seino Y. Expression of parathyroid hormone-related peptide messenger ribonucleic acid in developing kidney. Kidney Int 1999; 55(5):1696–1703.

    Article  PubMed  CAS  Google Scholar 

  40. Cebrian A, Garcia-Ocana A, Takane KK, Sipula D, Stewart AF, Vasavada RC. Overexpression of parathyroid hormone-related protein inhibits pancreatic beta-cell death in vivo and in vitro. Diabetes 2002; 51(10): 3003–3013.

    Article  PubMed  CAS  Google Scholar 

  41. Amizuka N, Warshawsky H, Henderson JE, Goltzman D, Karaplis AC. Parathyroid hormone-related peptide-depleted mice show abnormal epiphyseal cartilage development and altered endochondral bone formation. J Cell Biol 1994; 126(6):1611–1623.

    Article  PubMed  CAS  Google Scholar 

  42. Amizuka N, Karaplis AC, Henderson JE, Warshawsky H, Lipman ML, Matsuki Y, et al. Haploin-sufficiency of parathyroid hormone-related peptide (PTHrP) results in abnormal postnatal bone development. Dev Biol 1996; 175(1):166–176.

    Article  PubMed  CAS  Google Scholar 

  43. Fraher LJ, Avram R, Watson PH, Hendy GN, Henderson JE, Chong KL, et al. Comparison of the biochemical responses to human parathyroid hormone-(1-31)NH2 and hPTH-(1-34) in healthy humans. J Clin Endocrinol Metab 1999; 84(8):2739–2743.

    Article  PubMed  CAS  Google Scholar 

  44. Stewart AF, Horst R, Deftos LJ, Cadman EC, Lang R, Broadus AE. Biochemical evaluation of patients with cancer-associated hypercalcemia. Evidence for humoral and non-humoral groups. N Engl J Med 1980; 303: 1377–1381.

    Article  PubMed  CAS  Google Scholar 

  45. Murer H, Hernando N, Forster I, Biber J. Regulation of Na/Pi transporter in the proximal tubule. Annu Rev Physiol 2003; 65:531–542.

    Article  PubMed  CAS  Google Scholar 

  46. Henderson J, Bernier S, D’Amour P, Goltzman D. Effects of passive immunization against parathyroid hormone (PTH)-like peptide and PTH in hypercalcemic tumor-bearing rats and normocalcemic controls. Endocrinology 1990; 127(3):1310–1318.

    PubMed  CAS  Google Scholar 

  47. Horiuchi N, Caulfield MP, Fisher JE, Goldman ME, McKee RL, Reagan JE, et al. Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro. Science 1987; 238:1566–1568.

    Article  PubMed  CAS  Google Scholar 

  48. Schweitzer DH, Hamdy NA, Frolich M, Zwinderman AH, Papapoulos SE. Malignancy-associated hypercalcemia: resolution of controversies over vitamin D metabolism by a pathophysiological approach to the problem. Clin Endocrinol 1994; 41:251–256.

    CAS  Google Scholar 

  49. Rouleau MF, Mitchell J, Goltzman D. Characterization of the major parathyroid hormone target cell in the endosteal metaphysis of rat long bones. J Bone Miner Res 1990; 5(10):1043–1053.

    Article  PubMed  CAS  Google Scholar 

  50. Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, et al. TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T-cells. J Biol Chem 1997; 272: 25,190–25,194.

    Article  PubMed  CAS  Google Scholar 

  51. Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S-I, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis inhibitory factor and identical to TRANCE/RANKL. Proc Natl Acad Sci USA 1998; 95:3597–3602.

    Article  PubMed  CAS  Google Scholar 

  52. Lacey DM, Timms E, Tan H-L, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998; 93:165–176.

    Article  PubMed  CAS  Google Scholar 

  53. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997; 89:309–319.

    Article  PubMed  CAS  Google Scholar 

  54. Stewart AF, Vignery A, Silvergate A, Ravin ND, LiVolsi V, Broadus AE, et al. Quantitative bone histomorphometry in humoral hypercalcemia malignancy: uncoupling of bone cell activity. J Clin Endocrinol Metab 1982; 55:219–227.

    PubMed  CAS  Google Scholar 

  55. Powell GJ, Southby J, Danks JA, Stilwell RG, Haymen JA, Henderson MA, Bennett RC, et al. Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res 1991; 51:3059–3601.

    PubMed  CAS  Google Scholar 

  56. Sachmechi I, Kalra J, Molho L, Chawla K. Paraneoplastic hypercalcemia associated with uterine papillary serous carcinoma. Gynecol Oncol 1995; 58:378–382.

    Article  PubMed  CAS  Google Scholar 

  57. McAuley P, Asa SL, Chiu B, Henderson JE, Goltzman D, Drucker DJ. Parathyroid hormone-like peptide in normal and neoplastic mesothelial cells. Cancer 1990; 66:1975–1979.

    Article  PubMed  CAS  Google Scholar 

  58. Asa SL, Henderson JE, Goltzman D, Drucker DJ. Parathyroid hormone-like peptide in normal and neoplastic human endocrine tissues. J Clin Endocrinol Metab 1990; 71:1112–1118.

    PubMed  CAS  Google Scholar 

  59. Kimura S, Nishimura Y, Yamaguchi K, Nagaski K, Shimada K, Uchida H. A case of pheochromocytoma producing parathyroid hormone-related protein and presenting with hypercalcemia. J Clin Endocrinol Metab 1990; 70: 1559–1563.

    Article  PubMed  CAS  Google Scholar 

  60. Drucker DJ, Asa SL, Henderson JE, Goltzman D. The parathyroid hormone-like peptide gene is expressed in the normal and neoplastic human endocrine pancreas. Mol Endocrinol 1988; 3:1589–1595.

    Article  Google Scholar 

  61. Ikeda K, Arnold A, Magin M, Kinder B, Vydelingum NA, Brennan MR, et al. Expression of transcripts encoding a parathyroid hormone-related peptide in abnormal human parathyroid tissues. J Clin Endocrinol Metab 1989; 69:1240–1248.

    PubMed  CAS  Google Scholar 

  62. Ito M, Enomoto H, Usa T, Villadolid MC, Ohtsuru A, Namba H, et al. Expression of parathyroid hormone-related peptide in human pituitary tumors. J Clin Pathol 1993; 46:682,683.

    Article  Google Scholar 

  63. Nakashima M, Ohtsuru A, Luo WT, Nakayama T, Enomoto H, Usa T, et al. Expression of parathyroid hormone-related peptide in human thyroid tumors. J Pathol 1995; 175:227–236.

    Article  PubMed  CAS  Google Scholar 

  64. Kremer R, Shustik C, Tabak T, Papavasiliou V, Goltzman D. Parathyroid hormone-related peptide (PTHrP) in hematological malignancies. Am J Med 1996; 100:406–411.

    Article  PubMed  CAS  Google Scholar 

  65. Body JJ, Delmas PD. Urinary pyridinium cross-links as markers of bone resorption in tumor-associated hypercalcemia. J Clin Endocrinol Metab 1992; 74:471–475.

    Article  PubMed  CAS  Google Scholar 

  66. Rabbani SA, Haq M, Goltzman D. Biosynthesis and processing of endogenous parathyroid hormone-related peptide (PTHrP) by the rat Leydig cell tumor H-500. Biochemistry 1993; 32:4931–4937.

    Article  PubMed  CAS  Google Scholar 

  67. Yang KH, dePapp AE, Soifer NE, Dreyer BE, Wu TL, Porter SE, et al. Parathyroid hormone-related protein: Evidence for isoform and tissue-specific post-translational processing. Biochemistry 1994; 33: 7460–7469.

    Article  PubMed  CAS  Google Scholar 

  68. Budayr AA, Nissenson RA, Klein RF, Pun KK Clark OH, Diep D, Arnaud CD, Strewler GJ. Increased serum levels of a parathyroid hormone-like protein in malignancy-associated hypercalcemia. Ann Intern Med 1989; 111: 807–812.

    PubMed  CAS  Google Scholar 

  69. Henderson JE, Shustik C, Kremer R, Rabbani SA, Hendy GN, Goltzman D. Circulating concentrations of parathyroid hormone-like peptide in malignancy and hyperparathroidism. J Bone Miner Res 1990; 5: 105–113.

    PubMed  CAS  Google Scholar 

  70. Burtis WJ, Dann P, Gaich GA, Soifer NE. A high abundance midregion species of parathyroid hormone-related protein: immunological and chromatographic characterization in plasma. J Clin Endrocinol Metab 1994; 78: 317–322.

    Article  CAS  Google Scholar 

  71. Burtis WJ, Brady TG, Orloff JJ, Ersbak JB, Warrell RP, Olson BR, et al. Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. N Engl J Med 1990; 322:1106–1112.

    Article  PubMed  CAS  Google Scholar 

  72. Ratcliffe WA, Norbury S, Stott RA, Heath DA, Ratcliffe JG. Immunoreactivity of plasma parathyrin-related peptide: three region-specific radioimmunoassays and a two-site immunoradiometric assay compared. Clin Chem 1991; 37:1781–1787.

    PubMed  CAS  Google Scholar 

  73. Truong NU, deB Edwardes MD, Papavasiliou V, Goltzman D, Kremer R. Parathyroid hormone-related peptide and survival patients with cancer and hypercalcemia. AM J Med 2003; 115(2):115–121.

    Article  PubMed  CAS  Google Scholar 

  74. Body JJ. Hypercalcemia of malignancy. Semin Nephrol 2004; 24(1):48–54.

    Article  PubMed  Google Scholar 

  75. Sexton PM, Findlay DM, Martin TJ. Calcitonin. Curr Med Chem 1999; 6(11):1067–1093.

    PubMed  CAS  Google Scholar 

  76. Aklilu F, Park M, Goltzman D, Rabbini SA. Induction of parathyroid hormone-related peptide by the Ras oncogene: role of Ras farnesylation inhibitors as potential therapeutic agents for hypercalcemia of malignancy. Cancer Res 1997; 57(20):4517–4522.

    PubMed  CAS  Google Scholar 

  77. Liu B, Amizuka N, Goltzman D, Rabbani SA. Inhibition of processing of parathyroid hormone-related peptide by antisense furin; Effect in vitro and in vivo on rat Leydig (H-500) tumor cells. Int J Cancer 1995; 63: 1–6.

    Article  Google Scholar 

  78. Yu J, Papavasiliou V, Rhim J, Goltzman D, Kremer R. Vitamin D analogs: new therapeutic agents for the treatment of squamous cancer and its associated hypercalcemia. Anti Cancer Drugs 1995; 6:101–108.

    Article  PubMed  CAS  Google Scholar 

  79. Kukreja SC, Shevrin DH, Wimbiscus SA, Ebeling PR, Danks JA, Rodda CP, et al. Antibodies to parathyroid hormone-related protein lower serum calcium in athymic mouse models of malignancy-associated hypercalcemia due to human tumors. J Clin Invest 1988; 82:1798–1802.

    Article  PubMed  CAS  Google Scholar 

  80. Sato K, Onuma E, Yocum RC, Ogata E. Treatment of malignancy-associated hypercalcemia and cachexia with humanized anti-parathyroid hormone-related protein antibody. Semin Oncol 2003; 30(5);167–173.

    Article  PubMed  CAS  Google Scholar 

  81. Hofbauer LC, Neubauer A, Heufelder AE. Receptor activator of nuclear factor-kappaB ligand and osteoprotegerin: potential implications for the pathogenesis and treatment of malignant bone diseases. Cancer 2001; 92(3): 460–470.

    Article  PubMed  CAS  Google Scholar 

  82. Lipton A. Bisphosphonate therapy in the oncology setting. Expert Opin Emerg Drugs 2003; 8(2):469–488.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, McGill University, Montreal, Quebec, Canada

    David Goltzman MD

Authors
  1. David Goltzman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pathology and Molecular Medicine/Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada

    Gurmit Singh PhD

  2. Calcium Research Laboratory, McGill University Health Centre, Montreal, Quebec, Canada

    Shafaat A. Rabbani MD

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Goltzman, D. (2005). Parathyroid Hormone-Related Peptide and Malignancy. In: Singh, G., Rabbani, S.A. (eds) Bone Metastasis. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59259-892-7:013

Download citation

  • DOI: https://doi.org/10.1385/1-59259-892-7:013

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-403-6

  • Online ISBN: 978-1-59259-892-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation