Skip to main content
SpringerLink
Log in
Book cover

Human Cell Transformation pp 161–178Cite as

Parathyroid Hormone-Related Protein (PTHrP): An Emerging Target in Cancer Progression and Metastasis

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1164))

Abstract

PTHrP was first discovered as the most common mediator of malignancy-associated hypercalcemia. Subsequently, the discovery of its ubiquitous expression in normal tissues unraveled its role as a physiological autocrine/paracrine regulator. The significance of PTHrP in cancer is not confined to malignancy-associated hypercalcemia, and sufficient evidence now also supports its role in skeletal metastasis through its modulation of bone turnover. Furthermore, our own studies have recently shown the critical role of PTHrP in breast cancer initiation, growth, and metastasis. More recently, we have provided new evidence that overexpression of PTHrP is associated with higher incidence of brain metastasis and decreased overall survival in triple-negative breast cancer patients. Further mechanistic studies in human and mouse model are necessary to fully understand the role of PTHrP in tumor progression and metastasis.

This is a preview of subscription content, 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   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
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

Learn about institutional subscriptions

References

  1. Mundy, G. R., & Edwards, J. R. (2008). PTH-related peptide (PTHrP) in hypercalcemia. Journal of the American Society of Nephrology, 19, 672–675.

    Article  CAS  PubMed  Google Scholar 

  2. Powell, D., Singer, F. R., Murray, T. M., et al. (1973). Nonparathyroid humoral hypercalcemia in patients with neoplastic diseases. The New England Journal of Medicine, 289, 176–181.

    Article  CAS  PubMed  Google Scholar 

  3. Strewler, G. J., Stern, P. H., Jacobs, J. W., et al. (1987). Parathyroid hormonelike protein from human renal carcinoma cells. Structural and functional homology with parathyroid hormone. The Journal of Clinical Investigation, 80, 1803–1807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Burtis, W. J., Wu, T., Bunch, C., et al. (1987). Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. The Journal of Biological Chemistry, 262, 7151–7156.

    CAS  PubMed  Google Scholar 

  5. Moseley, J. M., Kubota, M., Diefenbach-Jagger, H., et al. (1987). Parathyroid hormone-related protein purified from a human lung cancer cell line. Proceedings of the National Academy of Sciences of the United States of America, 84, 5048–5052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Suva, L. J., Winslow, G. A., Wettenhall, R. E., et al. (1987). A parathyroid hormone-related protein implicated in malignant hypercalcemia: Cloning and expression. Science, 237, 893–896.

    Article  CAS  PubMed  Google Scholar 

  7. Mangin, M., Ikeda, K., Dreyer, B. E., et al. (1988). Two distinct tumor-derived, parathyroid hormone-like peptides result from alternative ribonucleic acid splicing. Molecular Endocrinology, 2, 1049–1055.

    Article  CAS  PubMed  Google Scholar 

  8. Thiede, M. A., Strewler, G. J., Nissenson, R. A., et al. (1988). Human renal carcinoma expresses two messages encoding a parathyroid hormone-like peptide: Evidence for the alternative splicing of a single-copy gene. Proceedings of the National Academy of Sciences of the United States of America, 85, 4605–4609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yasuda, T., Banville, D., Hendy, G. N., et al. (1989). Characterization of the human parathyroid hormone-like peptide gene. Functional and evolutionary aspects. The Journal of Biological Chemistry, 264, 7720–7725.

    CAS  PubMed  Google Scholar 

  10. Martin, T. J. (2016). Parathyroid hormone-related protein, its regulation of cartilage and bone development, and role in treating bone diseases. Physiological Reviews, 96, 831–871.

    Article  CAS  PubMed  Google Scholar 

  11. Mangin, M., Ikeda, K., & Broadus, A. E. (1990). Structure of the mouse gene encoding parathyroid hormone-related peptide. Gene, 95, 195–202.

    Article  CAS  PubMed  Google Scholar 

  12. Karaplis, A. C., Yasuda, T., Hendy, G. N., et al. (1990). Gene-encoding parathyroid hormone-like peptide: Nucleotide sequence of the rat gene and comparison with the human homologue. Molecular Endocrinology, 4, 441–446.

    Article  CAS  PubMed  Google Scholar 

  13. Thiede, M. A., & Rutledge, S. J. (1990). Nucleotide sequence of a parathyroid hormone-related peptide expressed by the 10 day chicken embryo. Nucleic Acids Research, 18, 3062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Power, D. M., Ingleton, P. M., Flanagan, J., et al. (2000). Genomic structure and expression of parathyroid hormone-related protein gene (PTHrP) in a teleost, Fugu rubripes. Gene, 250, 67–76.

    Article  CAS  PubMed  Google Scholar 

  15. Orloff, J. J., Wu, T. L., & Stewart, A. F. (1989). Parathyroid hormone-like proteins: Biochemical responses and receptor interactions. Endocrine Reviews, 10, 476–495.

    Article  CAS  PubMed  Google Scholar 

  16. Karaplis, A. C., & Goltzman, D. (2000). PTH and PTHrP effects on the skeleton. Reviews in Endocrine & Metabolic Disorders, 1, 331–341.

    Article  CAS  Google Scholar 

  17. Ohshima, K., Takeda, S., Hirose, M., et al. (2012). Structure-function relationship of the nuclear localization signal sequence of parathyroid hormone-related protein. Biomedical Research, 33, 191–199.

    Article  CAS  PubMed  Google Scholar 

  18. Lam, M. H., Thomas, R. J., Martin, T. J., et al. (2000). Nuclear and nucleolar localization of parathyroid hormone-related protein. Immunology and Cell Biology, 78, 395–402.

    Article  CAS  PubMed  Google Scholar 

  19. Lam, M. H., Hu, W., Xiao, C. Y., et al. (2001). Molecular dissection of the importin beta1-recognized nuclear targeting signal of parathyroid hormone-related protein. Biochemical and Biophysical Research Communications, 282, 629–634.

    Article  CAS  PubMed  Google Scholar 

  20. Cingolani, G., Bednenko, J., Gillespie, M. T., et al. (2002). Molecular basis for the recognition of a nonclassical nuclear localization signal by importin beta. Molecular Cell, 10, 1345–1353.

    Article  CAS  PubMed  Google Scholar 

  21. Massfelder, T., Dann, P., Wu, T. L., et al. (1997). Opposing mitogenic and anti-mitogenic actions of parathyroid hormone-related protein in vascular smooth muscle cells: A critical role for nuclear targeting. Proceedings of the National Academy of Sciences of the United States of America, 94, 13630–13635.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Soki, F. N., Park, S. I., & McCauley, L. K. (2012). The multifaceted actions of PTHrP in skeletal metastasis. Future Oncology, 8, 803–817.

    Article  CAS  PubMed  Google Scholar 

  23. Fenton, A. J., Kemp, B. E., Hammonds, R. G., Jr., et al. (1991). A potent inhibitor of osteoclastic bone resorption within a highly conserved pentapeptide region of parathyroid hormone-related protein; PTHrP[107-111]. Endocrinology, 129, 3424–3426.

    Article  CAS  PubMed  Google Scholar 

  24. Fenton, A. J., Kemp, B. E., Kent, G. N., et al. (1991). A carboxyl-terminal peptide from the parathyroid hormone-related protein inhibits bone resorption by osteoclasts. Endocrinology, 129, 1762–1768.

    Article  CAS  PubMed  Google Scholar 

  25. Fenton, A. J., Martin, T. J., & Nicholson, G. C. (1994). Carboxyl-terminal parathyroid hormone-related protein inhibits bone resorption by isolated chicken osteoclasts. Journal of Bone and Mineral Research, 9, 515–519.

    Article  CAS  PubMed  Google Scholar 

  26. de Miguel, F., Fiaschi-Taesch, N., López-Talavera, J. C., et al. (2001). The C-terminal region of PTHrP, in addition to the nuclear localization signal, is essential for the intracrine stimulation of proliferation in vascular smooth muscle cells. Endocrinology, 142, 4096–4105.

    Article  PubMed  Google Scholar 

  27. Budayr, A. A., Halloran, B. P., King, J. C., et al. (1989). High levels of a parathyroid hormone-like protein in milk. Proceedings of the National Academy of Sciences of the United States of America, 86, 7183–7185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kovacs, C. S., Lanske, B., Hunzelman, J. L., et al. (1996). Parathyroid hormone-related peptide (PTHrP) regulates fetal-placental calcium transport through a receptor distinct from the PTH/PTHrP receptor. Proceedings of the National Academy of Sciences of the United States of America, 93, 15233–15238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wysolmerski, J. J. (2012). Parathyroid hormone-related protein: An update. The Journal of Clinical Endocrinology and Metabolism, 97, 2947–2956.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wysolmerski, J. J., Cormier, S., Philbrick, W. M., et al. (2001). Absence of functional type 1 parathyroid hormone (PTH)/PTH-related protein receptors in humans is associated with abnormal breast development and tooth impaction. The Journal of Clinical Endocrinology and Metabolism, 86, 1788–1794.

    CAS  PubMed  Google Scholar 

  31. Hens, J. R., & Wysolmerski, J. J. (2005). Key stages of mammary gland development: Molecular mechanisms involved in the formation of the embryonic mammary gland. Breast Cancer Research, 7, 220–224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hens, J., Dann, P., Hiremath, M., et al. (2009). Analysis of gene expression in PTHrP−/− mammary buds supports a role for BMP signaling and MMP2 in the initiation of ductal morphogenesis. Developmental Dynamics, 238, 2713–2724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hens, J. R., Dann, P., Zhang, J. P., et al. (2007). BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction. Development, 134, 1221–1230.

    Article  CAS  PubMed  Google Scholar 

  34. Karaplis, A. C., Luz, A., Glowacki, J., et al. (1994). Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene. Genes & Development, 8, 277–289.

    Article  CAS  Google Scholar 

  35. Schipani, E., Langman, C., Hunzelman, J., et al. (1999). A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in Jansen’s metaphyseal chondrodysplasia. The Journal of Clinical Endocrinology and Metabolism, 84, 3052–3057.

    CAS  PubMed  Google Scholar 

  36. Schipani, E., Lanske, B., Hunzelman, J., et al. (1997). Targeted expression of constitutively active receptors for parathyroid hormone and parathyroid hormone-related peptide delays endochondral bone formation and rescues mice that lack parathyroid hormone-related peptide. Proceedings of the National Academy of Sciences of the United States of America, 94, 13689–13694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Weir, E. C., Philbrick, W. M., Amling, M., et al. (1996). Targeted overexpression of parathyroid hormone-related peptide in chondrocytes causes chondrodysplasia and delayed endochondral bone formation. Proceedings of the National Academy of Sciences of the United States of America, 93, 10240–10245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lanske, B., Karaplis, A. C., Lee, K., et al. (1996). PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth. Science, 273, 663–666.

    Article  CAS  PubMed  Google Scholar 

  39. Jobert, A. S., Zhang, P., Couvineau, A., et al. (1998). Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia. The Journal of Clinical Investigation, 102, 34–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Miao, D., Su, H., He, B., et al. (2008). Severe growth retardation and early lethality in mice lacking the nuclear localization sequence and C-terminus of PTH-related protein. Proceedings of the National Academy of Sciences of the United States of America, 105, 20309–20314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Amizuka, N., Warshawsky, H., Henderson, J. E., et al. (1994). Parathyroid hormone-related peptide-depleted mice show abnormal epiphyseal cartilage development and altered endochondral bone formation. The Journal of Cell Biology, 126, 1611–1623.

    Article  CAS  PubMed  Google Scholar 

  42. Amizuka, N., Karaplis, A. C., Henderson, J. E., et al. (1996). Haploinsufficiency of parathyroid hormone-related peptide (PTHrP) results in abnormal postnatal bone development. Developmental Biology, 175, 166–176.

    Article  CAS  PubMed  Google Scholar 

  43. Guise, T. A., Kozlow, W. M., Heras-Herzig, A., et al. (2005). Molecular mechanisms of breast cancer metastases to bone. Clinical Breast Cancer, 5, S46–S53.

    Article  CAS  PubMed  Google Scholar 

  44. Yasuda, H., Shima, N., Nakagawa, N., et al. (1999). A novel molecular mechanism modulating osteoclast differentiation and function. Bone, 25, 109–113.

    Article  CAS  PubMed  Google Scholar 

  45. Sternlicht, H., & Glezerman, I. G. (2015). Hypercalcemia of malignancy and new treatment options. Therapeutics and Clinical Risk Management, 11, 1779–1788.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Ralston, S. H., Cowan, R. A., Robertson, A. G., et al. (1984). Circulating vitamin D metabolites and hypercalcaemia of malignancy. Acta Endocrinologica, 106, 556–563.

    Article  CAS  PubMed  Google Scholar 

  47. Schweitzer, D. H., Hamdy, N. A., Frölich, M., et al. (1994). Malignancy-associated hypercalcaemia: Resolution of controversies over vitamin D metabolism by a pathophysiological approach to the syndrome. Clinical Endocrinology, 41, 251–256.

    Article  CAS  PubMed  Google Scholar 

  48. Donovan, P. J., Achong, N., Griffin, K., et al. (2015). PTHrP-mediated hypercalcemia: Causes and survival in 138 patients. The Journal of Clinical Endocrinology and Metabolism, 100, 2024–2029.

    Article  CAS  PubMed  Google Scholar 

  49. Kremer, R., & Goltzman, D. (2017). Parathyroid hormone-related peptide and other mediators of skeletal manifestations of malignancy. In Principles of bone biology. Cambridge: Elsevier.

    Google Scholar 

  50. Kremer, R., Li, J., Camirand, A., & Karaplis, A. C. (2011). Parathyroid hormone related protein (PTHrP) in tumor progression. Advances in Experimental Medicine and Biology, 720, 145–160.

    Article  CAS  PubMed  Google Scholar 

  51. Truong, N. U., deB Edwardes, M. D., Papavasiliou, V., et al. (2003). Parathyroid hormone-related peptide and survival of patients with cancer and hypercalcemia. The American Journal of Medicine, 115, 115–121.

    Article  CAS  PubMed  Google Scholar 

  52. Hiraki, A., Ueoka, H., Bessho, A., et al. (2002). Parathyroid hormone-related protein measured at the time of first visit is an indicator of bone metastases and survival in lung carcinoma patients with hypercalcemia. Cancer, 95, 1706–1713.

    Article  CAS  PubMed  Google Scholar 

  53. Pecherstorfer, M., Schilling, T., Blind, E., et al. (1994). Parathyroid hormone-related protein and life expectancy in hypercalcemic cancer patients. The Journal of Clinical Endocrinology and Metabolism, 78, 1268–1270.

    CAS  PubMed  Google Scholar 

  54. Burtis, W. J., Brady, T. G., Orloff, J. J., et al. (1990). Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. The New England Journal of Medicine, 322, 1106–1112.

    Article  CAS  PubMed  Google Scholar 

  55. Otieno, B. A., Krause, C. E., Jones, A. L., et al. (2016). Cancer diagnostics via ultrasensitive multiplexed detection of parathyroid hormone-related peptides with a microfluidic immunoarray. Analytical Chemistry, 88, 9269–9275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Castellano, D., Sepulveda, J. M., García-Escobar, I., et al. (2011). The role of RANK-ligand inhibition in cancer: The story of denosumab. The Oncologist, 16, 136–145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ogata, E. (2000). Parathyroid hormone-related protein as a potential target of therapy for cancer-associated morbidity. Cancer, 88(12 Suppl), 2909–2911.

    Article  CAS  PubMed  Google Scholar 

  58. Vargo-Gogola, T., & Rosen, J. M. (2007). Modelling breast cancer: One size does not fit all. Nature Reviews. Cancer, 7, 659–672.

    Article  CAS  PubMed  Google Scholar 

  59. Badve, S., Dabbs, D. J., Schnitt, S. J., et al. (2011). Basal-like and triple-negative breast cancers: A critical review with an emphasis on the implications for pathologists and oncologists. Modern Pathology, 24, 157–167.

    Article  PubMed  Google Scholar 

  60. Assaker, G., Camirand, A., Sabri, S., et al. (2018). In silico gene expression analysis of PTHrP and its association with molecular subtypes and organ-specifıc metastasis in human triple-negative breast cancer [abstract]. In Proceedings of the 109th annual meeting of the American Association for Cancer Research; April 14–18. Chicago, IL: AACR. Abstract no. 2598.

    Google Scholar 

  61. Jézéquel, P., Frénel, J. S., Campion, L., et al. (2013). bc-GenExMiner 3.0: New mining module computes breast cancer gene expression correlation analyses. Database: The Journal of Biological Databases and Curation, 2013, bas060.

    Article  CAS  PubMed  Google Scholar 

  62. Bauer, K. R., Brown, M., Cress, R. D., et al. (2007). Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: A population-based study from the California cancer registry. Cancer, 109, 1721–1728.

    Article  PubMed  Google Scholar 

  63. Sorlie, T., Perou, C. M., Tibshirani, R., et al. (2001). Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proceedings of the National Academy of Sciences of the United States of America, 98, 10869–10874.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Viale, G. (2012). The current state of breast cancer classification. Annals of Oncology, 23(Suppl 10), x207–x210.

    Article  PubMed  Google Scholar 

  65. Abdulkarim, B. S., Cuartero, J., Hanson, J., et al. (2011). Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. Journal of Clinical Oncology, 29, 2852–2858.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Assaker, G., Camirand, A., Abdulkarim, B., et al. (2018). Identifıcation of PTHrP as a biomarker of short survival & brain metastasis in a tissue microarray retrospective analysis of triple-negative breast cancer [abstract]. In Proceedings of the 109th annual meeting of the American Association for Cancer Research; April 14–18. Chicago, IL: AACR. Abstract no. 2632.

    Google Scholar 

  67. Li, J., Karaplis, A. C., Huang, D. C., et al. (2011). PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target. The Journal of Clinical Investigation, 121, 4655–4669.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Bouizar, Z., Spyratos, F., Deytieux, S., et al. (1993). Polymerase chain reaction analysis of parathyroid hormone-related protein gene expression in breast cancer patients and occurrence of bone metastases. Cancer Research, 53, 5076–5078.

    CAS  PubMed  Google Scholar 

  69. Kohno, N., Kitazawa, S., Fukase, M., et al. (1994). The expression of parathyroid hormone-related protein in human breast cancer with skeletal metastases. Surgery Today, 24, 215–220.

    Article  CAS  PubMed  Google Scholar 

  70. Linforth, R., Anderson, N., Hoey, R., et al. (2002). Coexpression of parathyroid hormone related protein and its receptor in early breast cancer predicts poor patient survival. Clinical Cancer Research, 8, 3172–3177.

    CAS  PubMed  Google Scholar 

  71. Takagaki, K., Takashima, T., Onoda, N., et al. (2012). Parathyroid hormone-related protein expression, in combination with nodal status, predicts bone metastasis and prognosis of breast cancer patients. Experimental and Therapeutic Medicine, 3, 963–968.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Xu, C., Wang, Z., Cui, R., et al. (2015). Co-expression of parathyroid hormone related protein and TGF-beta in breast cancer predicts poor survival outcome. BMC Cancer, 15, 925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Henderson, M. A., Danks, J. A., Slavin, J. L., et al. (2006). Parathyroid hormone-related protein localization in breast cancers predict improved prognosis. Cancer Research, 66, 2250–2256.

    Article  CAS  PubMed  Google Scholar 

  74. Fleming, N. I., Trivett, M. K., George, J., et al. (2009). Parathyroid hormone-related protein protects against mammary tumor emergence and is associated with monocyte infiltration in ductal carcinoma in situ. Cancer Research, 69, 7473–7479.

    Article  CAS  PubMed  Google Scholar 

  75. Ghoussaini, M., Fletcher, O., Michailidou, K., et al. (2012). Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nature Genetics, 44, 312–318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Kim, W., Takyar, F. M., Swan, K., et al. (2016). Calcium-sensing receptor promotes breast cancer by stimulating Intracrine actions of parathyroid hormone-related protein. Cancer Research, 76, 5348–5360.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Hollern, D. P., Swiatnicki, M. R., & Andrechek, E. R. (2018). Histological subtypes of mouse mammary tumors reveal conserved relationships to human cancers. PLoS Genetics, 14, e1007135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Johnson, R. W., Sun, Y., Ho, P. W. M., et al. (2018). Parathyroid hormone-related protein negatively regulates tumor cell dormancy genes in a PTHR1/cyclic AMP-independent manner. Frontiers in Endocrinology (Lausanne), 9, 241.

    Article  Google Scholar 

  79. Lin, E. Y., Jones, J. G., Li, P., et al. (2003). Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases. The American Journal of Pathology, 163, 2113–2126.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Dilworth, S. M. (2002). Polyoma virus middle T antigen and its role in identifying cancer-related molecules. Nature Reviews. Cancer, 2, 951–956.

    Article  CAS  PubMed  Google Scholar 

  81. Fluck, M. M., & Schaffhausen, B. S. (2009). Lessons in signaling and tumorigenesis from polyomavirus middle T antigen. Microbiology and Molecular Biology Reviews, 73, 542–563.

    Article  CAS  PubMed  Google Scholar 

  82. Wagner, K. U., McAllister, K., Ward, T., et al. (2001). Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice. Transgenic Research, 10, 545–553.

    Article  CAS  PubMed  Google Scholar 

  83. He, B., Deckelbaum, R. A., Miao, D., et al. (2001). Tissue-specific targeting of the pthrp gene: The generation of mice with floxed alleles. Endocrinology, 142, 2070–2077.

    Article  CAS  PubMed  Google Scholar 

  84. Muzumdar, M. D., Tasic, B., Miyamichi, K., et al. (2007). A global double-fluorescent Cre reporter mouse. Genesis, 45, 593–605.

    Article  CAS  PubMed  Google Scholar 

  85. Zhang, R., Li, J., Badescu, D., et al. (2018). PTHrP drives tumor initiation signaling pathways in the PyMT model of breast cancer progression [abstract]. In Proceedings of the 109th annual meeting of the American Association for Cancer Research; 2018 April 14–18. Chicago IL: AACR. Abstract no. 1995.

    Google Scholar 

  86. Paget, S. (1989). The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Reviews, 8, 98–101.

    CAS  PubMed  Google Scholar 

  87. McCauley, L. K., & Martin, T. J. (2012). Twenty-five years of PTHrP progress: From cancer hormone to multifunctional cytokine. Journal of Bone and Mineral Research, 27, 1231–1239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Li, X., Loberg, R., Liao, J., et al. (2009). A destructive cascade mediated by CCL2 facilitates prostate cancer growth in bone. Cancer Research, 69, 1685–1692.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Yin, J. J., Selander, K., Chirgwin, J. M., et al. (1999). TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. The Journal of Clinical Investigation, 103, 197–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Johnson, R. W., Finger, E. C., Olcina, M. M., et al. (2016). Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow. Nature Cell Biology, 18, 1078–1089.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Rostami, R., Mittal, S., Rostami, P., et al. (2016). Brain metastasis in breast cancer: A comprehensive literature review. Journal of Neuro-Oncology, 127, 407–414.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from the Canadian Institutes for Health Research (CIHR MOP142287; MOP130370) and the U.S. Department of Defense Breast Cancer Research Program (W81XWH-15-1-0723) to R. Kremer.

Author information

Authors and Affiliations

  1. Department of Medicine, McGill University Health Centre, Montréal, QC, Canada

    Rui Zhang, Jiarong Li, Anne Camirand & Richard Kremer

  2. Department of Pathology, McGill University Health Centre, Montréal, QC, Canada

    Gloria Assaker & Siham Sabri

  3. Lady Davis Institute for Medical Research, Montréal, QC, Canada

    Andrew C. Karaplis

Authors
  1. Rui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiarong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gloria Assaker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anne Camirand
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Siham Sabri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrew C. Karaplis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Richard Kremer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard Kremer .

Editor information

Editors and Affiliations

  1. Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

    Johng S. Rhim

  2. Georgetown University Medical Center, Washington, DC, USA

    Anatoly Dritschilo

  3. Department of Medicine, McGill University Health Centre, Montréal, QC, Canada

    Richard Kremer

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Zhang, R. et al. (2019). Parathyroid Hormone-Related Protein (PTHrP): An Emerging Target in Cancer Progression and Metastasis. In: Rhim, J., Dritschilo, A., Kremer, R. (eds) Human Cell Transformation. Advances in Experimental Medicine and Biology, vol 1164. Springer, Cham. https://doi.org/10.1007/978-3-030-22254-3_13

Download citation

Publish with us

Policies and ethics

Search

Navigation