Physiopathology of spine metastasis

Giulio Maccauro, Maria Silvia Spinelli, Sigismondo Mauro, Carlo Perisano, Calogero Graci, Michele Attilio Rosa, Giulio Maccauro, Maria Silvia Spinelli, Sigismondo Mauro, Carlo Perisano, Calogero Graci, Michele Attilio Rosa

Abstract

The metastasis is the spread of cancer from one part of the body to another. Two-thirds of patients with cancer will develop bone metastasis. Breast, prostate and lung cancer are responsible for more than 80% of cases of metastatic bone disease. The spine is the most common site of bone metastasis. A spinal metastasis may cause pain, instability and neurological injuries. The diffusion through Batson venous system is the principal process of spinal metastasis, but the dissemination is possible also through arterial and lymphatic system or by contiguity. Once cancer cells have invaded the bone, they produce growth factors that stimulate osteoblastic or osteolytic activity resulting in bone remodeling with release of other growth factors that lead to a vicious cycle of bone destruction and growth of local tumour.

Figures

Figure 1
Figure 1
Batson venous plexus, from Batson O.V., “The function of the vertebral veins and their role in the spread of metastases,” Ann Surg. 1940 July; 112 (1): 138–149.
Figure 2
Figure 2
Receptor Activator of Nuclear Factor k B Ligand (RANK) and Osteoclast Formation, from Roodman G. D., “Mechanisms of bone metastasis,” N Engl J Med., 15; 350 (16): 1655–64, Apr 2004.
Figure 3
Figure 3
The Vicious Circle of Osteolytic Metastasis, from Roodman G. D., “Mechanisms of bone metastasis,” N Engl J Med., 15; 350 (16): 1655–64, Apr 2004.

References

    1. Hosono N, Yonenobu K, Fuji T, Ebara S, Yamashita K, Ono K. Orthopaedic management of spinal metastases. Clinical Orthopaedics and Related Research. 1995;(312):148–159.
    1. Shaw B, Mansfield FL, Borges L. One-stage posterolateral decompression and stabilization for primary and metastatic vertebral tumors in the thoracic and lumbar spine. Journal of Neurosurgery. 1989;70(3):405–410.
    1. Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nature Reviews Cancer. 2002;2(8):584–593.
    1. Piccioli A, Capanna R. Il Trattamento delle Metastasi Ossee. 2008. (Linee Guida SIOT).
    1. Yasuda H, Shima N, Nakagawa N, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(7):3597–3602.
    1. Francis KC, Hutter RV. Neoplasms of the spine in the aged. Clinical Orthopaedics and Related Research. 1963;26:54–66.
    1. Mirra JM. Bone Tumors: Clinical, Radiologic, and Pathologic Correlation. Philadelphia, Pa, USA: Lea and Febiger; 1989.
    1. Boland PJ, Lane JM, Sundaresan N. Metastatic disease of the spine. Clinical Orthopaedics and Related Research. 1982;169:95–102.
    1. Coleman RE, Roodman, Smith, Body, Suva, Vessella Clinical features of metastatic bone disease and risk of skeletal morbidity. Clinical Cancer Research. 2006;12(20):6243s–6249s.
    1. Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG. Abeloff’s Clinical Oncology. 4th edition. Philadelphia, Pa, USA: Churchill Livngstone Elsevier; 2008.
    1. Roodman GD. Mechanisms of bone metastasis. The New England Journal of Medicine. 2004;350(16):1655–1698.
    1. Togawa D, Lewandrowsky KU. The pathophysiology of spinal metastases. In: McLain RF, editor. Cancer in the Spine. 2006. pp. 17–23. (Current Clinical Oncology).
    1. Bellahcène A, Maloujahmoum N, Fisher LW, et al. Expression of bone sialoprotein in human lung cancer. Calcified Tissue International. 1997;61(3):183–188.
    1. Vargas SJ, Gillespie MT, Powell GJ, et al. Localization of parathyroid hormone-related protein mRNA expression in breast cancer and metastatic lesions by in situ hybridization. Journal of Bone and Mineral Research. 1992;7(8):971–979.
    1. Smid M, Wang Y, Klijn JGM, et al. Genes associated with breast cancer metastatic to bone. Journal of Clinical Oncology. 2006;24(15):2261–2267.
    1. Black P. Spinal metastasis: current status and recommended guidelines for management. Neurosurgery. 1979;5(6):726–746.
    1. Harrington KD. Orthopedic surgical management of skeletal complications of malignancy. Cancer. 1997;80(supplement 8):1614–1627.
    1. Sundaresan N, Digiacinto GV, Hughes JEO, Cafferty M, Vallejo A. Treatment of neoplastic spinal cord compression: results of a prospective study. Neurosurgery. 1991;29(5):645–650.
    1. Algra PR, Heimans JJ, Valk J, Nauta JJ, Lachniet M, Van Kooten B. Do metastases in vertebrae begin in the body or the pedicles? Imaging study in 45 patients. The American Journal of Roentgenology. 1992;158(6):1275–1279.
    1. Jaffe WF. Tumors and Timorous Conditions of the Bones and Joints. Philadelphia, Pa, USA: Lea and Febiger; 1958.
    1. Batson OV. The role of the vertebral veins in metastatic processes. Annals of Internal Medicine. 1942;16:38–45.
    1. Galasko CSB. Mechanisms of bone destruction in the development of skeletal metastases. Nature. 1976;263(5577):507–508.
    1. Gilbert RW, Kim JH, Posner JB. Epidural spinal cord compression from metastatic tumor: diagnosis and treatment. Annals of Neurology. 1978;3(1):40–45.
    1. Krishnamurthy GT, Tubis M, Hiss J, Blahd WH. Distribution pattern of metastatic bone disease. A need for total body skeletal image. Journal of the American Medical Association. 1977;237(23):2504–2506.
    1. Schaberg J, Gainor BJ. A profile of metastatic carcinoma of the spine. Spine. 1985;10(1):19–20.
    1. Brihaye J, Ectors P, Lemort M, Van Houtte P. The management of spinal epidural metastases. Advances and Technical Standards in Neurosurgery. 1988;16:121–176.
    1. American Cancer Society. Cancer Facts and Figures. Atlanta, Ga, USA: American cancer Society; 2007.
    1. Batson OV. The function of the vertebral veins and their role in the spread of metastases. 1940. Clinical Orthopaedics and Related Research. 1995;(312):4–9.
    1. Harrington KD. Metastatic disease of the spine. Journal of Bone and Joint Surgery. 1986;68(7):1110–1115.
    1. Coman DR, de Long RP. The role of the vertebral venous system in the metastasis of cancer to the spinal column; experiments with tumor-cell suspensions in rats and rabbits. Cancer. 1951;4(3):610–618.
    1. Crock HV, Yoshizawa H, Kame SK. Observations on the venous drainage of the human vertebral body. Journal of Bone and Joint Surgery. 1973;55(3):528–533.
    1. Louis R, Ouiminga RM, Obounou D. The azygos or vertebro-parietal venous anastomotic system. Bulletin de l’Association des Anatomistes. 1976;60(169):381–397.
    1. Nagasaka A, Miyamoto T, Yoshizaki H, et al. Vertebral bone metastasis of small cell carcinoma of lung in a diabetic patient, initially diagnosed as pyogenic vertebral osteomyelitis. Diabetes Research. 1993;22(3):135–144.
    1. Arguello F, Baggs RB, Duerst RE, Johnstone L, McQueen K, Frantz CN. Pathogenesis of vertebral metastasis and epidural spinal cord compression. Cancer. 1990;65(1):98–106.
    1. Bonucci E. Physiopathology of cancer metastases in bone and of the changes they induce in bone remodeling. ATTI Della Accademia Nazionale Dei Lincei Rendiconti Lincei Scienze Fisiche E Naturali. 2002;13(3):181–246.
    1. Kurschat P, Mauch C. Mechanisms of metastasis. Clinical and Experimental Dermatology. 2000;25(6):482–489.
    1. Orr FW, Lee J, Duivenvoorden WCM, Singh G. Pathophysiologic interactions in skeletal metastasis. Cancer. 2000;88(12):2912–2918.
    1. DeClerck YA. Interactions between tumour cells and stromal cells and proteolytic modification of the extracellular matrix by metalloproteinases in cancer. The European Journal of Cancer. 2000;36(10):1258–1268.
    1. Starkey JR. Cell-matrix interactions during tumor invasion. Cancer and Metastasis Reviews. 1990;9(2):113–123.
    1. Stetler-Stevenson WG, Liotta LA, Kleiner DE. Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis. FASEB Journal. 1993;7(15):1434–1441.
    1. Duffy MJ. The role of proteolytic enzymes in cancer invasion and metastasis. Clinical and Experimental Metastasis. 1992;10(3):145–155.
    1. Ray JM, Stetler-Stevenson WG. The role of matrix metalloproteases and their inhibitors in tumor invasion, metastasis and angiogenesis. The European Respiratory Journal. 1994;7(11):2062–2072.
    1. Rémy L. Données récentes sur les métalloprotéinases, acteurs incontournables de la progression tumorale. Pathologie Biologie. 1997;45(9):759–765.
    1. Ellerbroek SM, Stack MS. Membrane associated matrix metalloproteinases in metastasis. BioEssays. 1999;21(11):940–949.
    1. Kleiner DE, Stetler-Stevenson WG. Matrix metalloproteinases and metastasis. Cancer Chemotherapy & Pharmacology. 1999;43:S42–S51.
    1. Johansson N, Ahonen M, Kähäri VM. Matrix metalloproteinases in tumor invasion. Cellular and Molecular Life Sciences. 2000;57(1):5–15.
    1. Johansson N, Kahari VM. Matrix metalloproteinases in squamous cell carcinoma. Histology and Histopathology. 2000;15:225–237.
    1. Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM. Matrix metalloproteinases: biologic activity and clinical implications. Journal of Clinical Oncology. 2000;18(5):1135–1149.
    1. Chang C, Werb Z. The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends in Cell Biology. 2001;11(11):S37–S43.
    1. Foda HD, Zucker S. Matrix metalloproteinases in cancer invasion, metastasis and angiogenesis. Drug Discovery Today. 2001;6(9):478–482.
    1. John A, Tuszynski G. The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. Pathology and Oncology Research. 2001;7(1):14–23.
    1. Mauch C, Krieg T, Bauer EA. Role of the extracellular matrix in the degradation of connective tissue. Archives of Dermatological Research. 1994;287(1):107–114.
    1. Angelucci A, D’Ascenzo S, Festuccia C, et al. Vesicle-associated urokinase plasminogen activator promotes invasion in prostate cancer cell lines. Clinical and Experimental Metastasis. 2000;18(2):163–170.
    1. Hart CA, Scott LJ, Bagley S, Bryden AAG, Clarke NW, Lang SH. Role of proteolytic enzymes in human prostate bone metastasis formation: in vivo and in vitro studies. The British Journal of Cancer. 2002;86(7):1136–1142.
    1. Stamenkovic I. Matrix metalloproteinases in tumor invasion and metastasis. Seminars in Cancer Biology. 2000;10(6):415–433.
    1. Honn KV, Tang DG. Adhesion molecules and tumor cell interaction with endothelium and subendothelial matrix. Cancer and Metastasis Reviews. 1992;11(3-4):353–375.
    1. Johnson JP. Cell adhesion molecules of the immunoglobulin supergene family and their role in malignant transformation and progression to metastatic disease. Cancer and Metastasis Reviews. 1991;10(1):11–22.
    1. Tang DG, Honn KV. Adhesion molecules and tumor metastasis: an update. Invasion and Metastasis. 1994;14(1–6):109–122.
    1. Pantel K, Schlimok G, Angstwurm M, et al. Early metastasis of human solid tumours: expression of cell adhesion molecules. Ciba Foundation Symposium. 1995;189:157–170.
    1. Weiss L, Haydock K, Pickren JW, Lane WW. Organ vascularity and metastatic frequency. The American Journal of Pathology. 1980;101(1):101–114.
    1. Mundy GR. Mechanisms of bone metastasis. Cancer. 1997;80(8):1546–1556.
    1. Liaw L, Crawford HC. Functions of the extracellular matrix and matrix degrading proteases during tumor progression. Brazilian Journal of Medical and Biological Research. 1999;32(7):805–812.
    1. Goltzman D, Karaplis AC, Kremer R, Rabbani SA. Molecular basis of the spectrum of skeletal complications of neoplasia. Cancer. 2000;88(12):2903–2908.
    1. Rosol TJ. Pathogenesis of bone metastasis: role of tumor-related proteins. Journal of Bone and Mineral Research. 2000;15(5):844–850.
    1. Kelly T, Børset M, Abe E, Gaddy-Kurten D, Sanderson RD. Matrix metalloproteinases in multiple myeloma. Leukemia and Lymphoma. 2000;37(3-4):273–281.
    1. Bellahcène A, Bonjean K, Fohr B, et al. Bone sialoprotein mediates human endothelial cell attachment and migration and promotes angiogenesis. Circulation Research. 2000;86(8):885–891.
    1. Connolly DT, Heuvelman DM, Nelson R, et al. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. Journal of Clinical Investigation. 1989;84(5):1470–1478.
    1. Yin JJ, Pollock CB, Kelly K. Mechanisms of cancer metastasis to the bone. Cell Research. 2005;15(1):57–62.
    1. Lipton A. Pathophysiology of bone metastases: how this knowledge may lead to therapeutic intervention. Journal of Supportive Oncology. 2004;2(3):205–213.
    1. Siclari VA, Guise TA, Chirgwin JM. Molecular interactions between breast cancer cells and the bone microenvironment drive skeletal metastases. Cancer and Metastasis Reviews. 2006;25(4):621–633.
    1. Shevde N, Anklesaria P, Greenberger JS, Bleiberg I, Glowacki J. Stromal cell-mediated stimulation of osteoclastogenesis. Proceedings of the Society for Experimental Biology and Medicine. 1994;205(4):306–315.
    1. Greenberger JS. The pathophysiology and management of spine metastasis from lung cancer. Journal of Neuro-Oncology. 1995;23(2):109–120.
    1. Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM. Matrix metalloproteinases: biologic activity and clinical implications. Journal of Clinical Oncology. 2000;18(5):1135–1149.
    1. Roodman GD. Role of stromal-derived cytokines and growth factors in bone metastasis. Cancer. 2003;97(3):733–738.
    1. Rose AA, Siegel PM. Breast cancer-derived factors facilitate osteolytic bone metastasis. Bulletin du Cancer. 2006;93(9):931–943.
    1. Guise TA, Yin JJ, Taylor SD, et al. Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis. Journal of Clinical Investigation. 1996;98(7):1544–1549.
    1. Powell GJ, Southby J, Danks JA, et al. Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Research. 1991;51(11):3059–3061.
    1. Yin JJ, Selander K, Chirgwin JM, et al. TGF-β signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. Journal of Clinical Investigation. 1999;103(2):197–206.
    1. Hofbauer LC, Heufelder AE. The role of osteoprotegerin and receptor activator of nuclear factor kappaB ligand in the pathogenesis and treatment of rheumatoid arthritis. Arthritis & Rheumatism. 2001;44(2):253–259.
    1. Basolo F, Fiore L, Fontanini G, et al. Expression of and response to interleukin 6 (IL6) in human mammary tumors. Cancer Research. 1996;56(13):3118–3122.
    1. de La Mata J, Uy HL, Guise TA, et al. Interleukin-6 enhances hypercalcemia and bone resorption mediated by parathyroid hormone-related protein in vivo. Journal of Clinical Investigation. 1995;95(6):2846–2852.
    1. Guise TA, Mundy GR. Cancer and bone. Endocrine Reviews. 1998;19(1):18–54.
    1. Achbarou A, Kaiser S, Tremblay G, et al. Urokinase overproduction results in increased skeletal metastasis by prostate cancer cells in vivo. Cancer Research. 1994;54(9):2372–2377.
    1. Nelson JB, Hedican SP, George DJ, et al. Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nature Medicine. 1995;1(9):944–949.
    1. Chiao JW, Moonga BS, Yang YM, et al. Endothelin-1 from prostate cancer cells is enhanced by bone contact which blocks osteoclastic bone resorption. British Journal of Cancer. 2000;83(3):360–365.
    1. Nelson JB, Hedican SP, George DJ, et al. Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nature Medicine. 1995;1(9):944–949.
    1. Granchi S, Brocchi S, Bonaccorsi L, et al. Endothelin-1 production by prostate cancer cell lines is up-regulated by factors involved in cancer progression and down-regulated by androgens. Prostate. 2001;49(4):267–277.
    1. Yin JJ, Mohammad KS, Käkönen SM, et al. A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(19):10954–10959.
    1. Chikatsu N, Takeuchi Y, Tamura Y, et al. Interactions between cancer and bone marrow cells induce osteoclast differentiation factor expression and osteoclast-like cell formation in vitro. Biochemical and Biophysical Research Communications. 2000;267(2):632–637.
    1. Bryden AA, Hoyland JA, Freemont AJ, Clarke NW, George NJR. Parathyroid hormone related peptide and receptor expression in paired primary prostate cancer and bone metastases. The British Journal of Cancer. 2002;86(3):322–325.
    1. Clarke NW, McClure J, George NJR. Morphometric evidence for bone resorption and replacement in prostate cancer. The British Journal of Urology. 1991;68(1):74–80.
    1. Lee YP, Schwarz EM, Davies M, et al. Use of zoledronate to treat osteoblastic versus osteolytic lesions in a severe-combined-immunodeficient mouse model. Cancer Research. 2002;62(19):5564–5570.
    1. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annual Review of Cell and Developmental Biology. 2004;20:781–810.
    1. Hall CL, Keller ET. The role of Wnts in bone metastases. Cancer and Metastasis Reviews. 2006;25(4):551–558.
    1. Cramer SD, Chen Z, Peehl DM. Prostate specific antigen cleaves parathyroid hormone-related protein in the PTH-like domain: inactivation of PTHrP-stimulated cAMP accumulation in mouse osteoblasts. Journal of Urology. 1996;156(2):526–531.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir