The Emerging Role of Osteocytes in Cancer in Bone

Overview

Journal JBMR Plus

Publisher Oxford University Press

Date 2019 Mar 29

PMID 30918922

Citations 21

Authors

Emily G Atkinson

Jesus Delgado-Calle

Affiliations

Soon will be listed here.

Abstract

Advances in the last decade have established the osteocyte, the most abundant cell in bone, as a dynamic and multifunctional cell capable of controlling bone homeostasis by regulating the function of both osteoblasts and osteoclasts. In addition, accumulating evidence demonstrates that osteocyte function is altered in several skeletal disorders, and targeting osteocytes and their derived factors improves skeletal health. Despite the remarkable progress in our understanding of osteocyte biology, there has been a paucity of information regarding the role of osteocytes in the progression of cancer in bone. Exciting, recent discoveries suggest that tumor cells communicate with osteocytes to generate a microenvironment that supports the growth and survival of cancer cells and stimulates bone destruction. This review features these novel findings and discussions regarding the impact of chemotherapy on osteocyte function and the potential of targeting osteocytes for the treatment of cancer in bone. © 2019 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Citing Articles

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References

Manolagas S . Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000; 21(2):115-37. DOI: 10.1210/edrv.21.2.0395. View

Guise T . Molecular mechanisms of osteolytic bone metastases. Cancer. 2000; 88(12 Suppl):2892-8. DOI: 10.1002/1097-0142(20000615)88:12+<2892::aid-cncr2>3.0.co;2-y. View

Hauge E, Qvesel D, Eriksen E, Mosekilde L, Melsen F . Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res. 2001; 16(9):1575-82. DOI: 10.1359/jbmr.2001.16.9.1575. View

Pecheur I, Peyruchaud O, Serre C, Guglielmi J, Voland C, Bourre F . Integrin alpha(v)beta3 expression confers on tumor cells a greater propensity to metastasize to bone. FASEB J. 2002; 16(10):1266-8. DOI: 10.1096/fj.01-0911fje. View

Mundy G . Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002; 2(8):584-93. DOI: 10.1038/nrc867. View

Searfoss G, Jordan W, Calligaro D, Galbreath E, Schirtzinger L, Berridge B . Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor. J Biol Chem. 2003; 278(46):46107-16. DOI: 10.1074/jbc.M307757200. View

Frost H . In vivo osteocyte death. J Bone Joint Surg Am. 1960; 42-A:138-43. View

Cottler-Fox M, Lapidot T, Petit I, Kollet O, Dipersio J, Link D . Stem cell mobilization. Hematology Am Soc Hematol Educ Program. 2003; :419-37. DOI: 10.1182/asheducation-2003.1.419. View

Nefedova Y, Cheng P, Alsina M, Dalton W, Gabrilovich D . Involvement of Notch-1 signaling in bone marrow stroma-mediated de novo drug resistance of myeloma and other malignant lymphoid cell lines. Blood. 2003; 103(9):3503-10. DOI: 10.1182/blood-2003-07-2340. View

10.

Jundt F, Probsting K, Anagnostopoulos I, Muehlinghaus G, Chatterjee M, Mathas S . Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells. Blood. 2004; 103(9):3511-5. DOI: 10.1182/blood-2003-07-2254. View

11.

Parfitt A . Life history of osteocytes: relationship to bone age, bone remodeling, and bone fragility. J Musculoskelet Neuronal Interact. 2005; 2(6):499-500. View

12.

Keller H, Kneissel M . SOST is a target gene for PTH in bone. Bone. 2005; 37(2):148-58. DOI: 10.1016/j.bone.2005.03.018. View

13.

Bellido T, Ali A, Gubrij I, Plotkin L, Fu Q, OBrien C . Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology. 2005; 146(11):4577-83. DOI: 10.1210/en.2005-0239. View

14.

Poole K, van Bezooijen R, Loveridge N, Hamersma H, Papapoulos S, Lowik C . Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J. 2005; 19(13):1842-4. DOI: 10.1096/fj.05-4221fje. View

15.

McClung M, Lewiecki E, Cohen S, Bolognese M, Woodson G, Moffett A . Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006; 354(8):821-31. DOI: 10.1056/NEJMoa044459. View

16.

Obeng E, Carlson L, Gutman D, Harrington Jr W, Lee K, Boise L . Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood. 2006; 107(12):4907-16. PMC: 1895817. DOI: 10.1182/blood-2005-08-3531. View

17.

Aguirre J, Plotkin L, Stewart S, Weinstein R, Parfitt A, Manolagas S . Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. J Bone Miner Res. 2006; 21(4):605-15. DOI: 10.1359/jbmr.060107. View

18.

Klein M, Siegal G . Osteosarcoma: anatomic and histologic variants. Am J Clin Pathol. 2006; 125(4):555-81. DOI: 10.1309/UC6K-QHLD-9LV2-KENN. View

19.

Kollet O, Dar A, Shivtiel S, Kalinkovich A, Lapid K, Sztainberg Y . Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nat Med. 2006; 12(6):657-64. DOI: 10.1038/nm1417. View

20.

Giuliani N, Rizzoli V, Roodman G . Multiple myeloma bone disease: Pathophysiology of osteoblast inhibition. Blood. 2006; 108(13):3992-6. DOI: 10.1182/blood-2006-05-026112. View