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Interaktion von Tumorzellen und Knochen bei osteolytischen/osteosklerotischen Metastasen, Circulus vitiosus der Knochenmetastasierung

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Knochenmetastasen

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Zusammenfassung

Die Interaktion von Tumorzellen und Zellen des Knochens verstärkt den Prozess der ossären Metastasierung im Rahmen eines Circulus vitiosus. Tumorzellen sezernieren Faktoren wie RANKL und PTHrP, welche die Aktivität von Osteoklasten steigern. Dies führt zu einem verstärkten Knochenabbau und zur vermehrten Freisetzung von Wachstumsfaktoren aus der Knochenmatrix, was wiederum die Tumorprogression fördert. Dieses Kapitel beschreibt das Zusammenspiel zwischen Tumorzellen und Knochen und erläutert die zugrundeliegenden molekularen Grundlagen. Besonderer Bezug wird hierbei auf die Unterschiede zwischen osteosklerotischen und osteolytischen Metastasen genommen und auf mögliche therapeutische Ziele, die sich aus diesen Erkenntnissen ergeben.

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Literatur

  • Armstrong AP, Miller RE, Jones JC et al (2008) RANKL acts directly on RANK-expressing prostate tumor cells and mediates migration and expression of tumor metastasis genes. Prostate 68: 92–104

    Article  CAS  PubMed  Google Scholar 

  • Asadi F, Farraj M, Sharifi R et al (1996) Enhanced expression of parathyroid hormone-related protein in prostate cancer as compared with benign prostatic hyperplasia. Hum Pathol 27: 1319–1323

    Article  CAS  PubMed  Google Scholar 

  • Bendre MS, Montague DC, Peery T et al (2003) Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease. Bone 33: 28–37

    Article  CAS  PubMed  Google Scholar 

  • Bendre MS, Margulies AG, Walser B et al (2005) Tumor-derived interleukin-8 stimulates osteolysis independent of the receptor activator of nuclear factor-kappaB ligand pathway. Cancer Res 65: 11001–11009

    Article  CAS  PubMed  Google Scholar 

  • Benoy IH, Salgado R, Van Dam P et al (2004) Increased serum interleukin-8 in patients with early and metastatic breast cancer correlates with early dissemination and survival. Clin Cancer Res 10: 7157–7162

    Article  CAS  PubMed  Google Scholar 

  • Chen D, Zhao M, Mundy GR (2004) Bone morphogenetic proteins. Growth Factors 22: 233–241

    Article  CAS  PubMed  Google Scholar 

  • Chen G, Sircar K, Aprikian A et al (2006) Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation. Cancer 107: 289–298

    Article  CAS  PubMed  Google Scholar 

  • Cross SS, Harrison RF, Balasubramanian SP et al (2006) Expression of receptor activator of nuclear factor kappa beta ligand (RANKL) and tumour necrosis factor related, apoptosis inducing ligand (TRAIL) in breast cancer, and their relations with osteoprotegerin, oestrogen receptor, and clinicopathological variables. J Clin Pathol 59: 716–720

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dai J, Keller J, Zhang J et al (2005) Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. Cancer Res 65: 8274–8285

    Article  CAS  PubMed  Google Scholar 

  • Derynck R, Akhurst RJ, Balmain A (2001) TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 29: 117–129

    Article  CAS  PubMed  Google Scholar 

  • Feeley BT, Liu NQ, Conduah AH et al (2006) Mixed metastatic lung cancer lesions in bone are inhibited by noggin overexpression and Rank:Fc administration. J Bone Miner Res 21(10): 1571–1580

    Article  CAS  PubMed  Google Scholar 

  • Giuliani N, Bataille R, Mancini C et al (2001) Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment. Blood 15(98): 3527–3533

    Article  Google Scholar 

  • Gonzalez-Suarez E, Jacob AP, Jones J et al (2010) RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis. Nature 468: 103–107

    Article  CAS  PubMed  Google Scholar 

  • Gujral A, Burton DW, Terkeltaub R, Deftos LJ (2001) Parathyroid hormone-related protein induces interleukin 8 production by prostate cancer cells via a novel intracrine mechanism not mediated by its classical nuclear localization sequence. Cancer Res 61: 2282–2288

    CAS  PubMed  Google Scholar 

  • Gupta J, Robbins J, Jilling T, Seth P (2011) TGFβ-dependent induction of interleukin-11 and interleukin-8 involves SMAD and p38 MAPK pathways in breast tumor models with varied bone metastases potential. Cancer Biol Ther 11: 311–316

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hall CL, Kang S, MacDougald OA, Keller ET (2006) Role of Wnts in prostate cancer bone metastases. J Cell Biochem 97: 661–672

    Article  CAS  PubMed  Google Scholar 

  • Hanavadi S, Martin TA, Watkins G et al (2006) Expression of interleukin 11 and its receptor and their prognostic value in human breast cancer. Ann Surg Oncol 13: 802–808

    Article  PubMed  Google Scholar 

  • Heider U, Langelotz C, Jakob C et al (2003) Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma. Clin Cancer Res 9: 1436–1440

    CAS  PubMed  Google Scholar 

  • Hens JR, Dann P, Zhang JP 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 

  • Hofbauer LC, Schoppet M (2004) Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 292: 490–495

    Article  CAS  PubMed  Google Scholar 

  • Hofbauer LC, Rachner T, Singh SK (2008) Fatal attraction: why breast cancer cells home to bone. Breast Cancer Res 10: 101

    Article  PubMed Central  PubMed  Google Scholar 

  • Holen I, Cross SS, Neville-Webbe HL et al (2005) Osteoprotegerin (OPG) expression by breast cancer cells in vitro and breast tumours in vivo – a role in tumour cell survival? Breast Cancer Res Treat 92(3): 207–215

    Article  CAS  PubMed  Google Scholar 

  • Hsu H, Lacey DL, Dunstan CR et al (1999) Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Porc Natl Acad Sci USA 96: 3540–3545

    Article  CAS  Google Scholar 

  • Inoue K, Slaton JW, Eve BY et al (2000) Interleukin 8 expression regulates tumorigenicity and metastases in androgen-independent prostate cancer. Clin Cancer Res 6(5): 2104–2119

    CAS  PubMed  Google Scholar 

  • Jones DH, Nakashima T, Sanchez OH et al (2006) Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440: 692–696

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Kurihara N, Bertolini D, Suda T et al (1990) IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release. J Immunol 144: 4226–4230

    CAS  PubMed  Google Scholar 

  • Lacey DL, Timms E, Tan HL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93: 165–176

    Article  CAS  PubMed  Google Scholar 

  • Liao J, McCauley LK (2006) Skeletal metastasis: established and emerging roles of parathyroid hormone related protein (PTHrP). Cancer Metastasis Rev 25: 559–571

    Article  CAS  PubMed  Google Scholar 

  • Liao J, Li X, Koh AJ, Berry JE et al (2008) Tumor expressed PTHrP facilitates prostate cancer-induced osteoblastic lesions. Int J Cancer 123: 2267–2278

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liapis H, Crouch EC, Grosso LE et al (1993) Expression of parathyroid-like protein in normal, proliferative, and neoplastic human breast tissues. Am J Pathol 143: 1169–1178

    CAS  PubMed Central  PubMed  Google Scholar 

  • Morgan H, Tumber A, Hill PA (2004) Breast cancer cells induce osteoclast formation by stimulating host IL-11 production and downregulating granulocyte/macrophage colony-stimulating factor. Int J Cancer 109: 653–660

    Article  CAS  PubMed  Google Scholar 

  • Morony S, Capparelli C, Sarosi I et al (2001) Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis. Cancer Res 61: 4432–4436

    CAS  PubMed  Google Scholar 

  • Nakashima T, Hayashi M, Fukunaga T et al (2011) Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med 17: 1231–1234

    Article  CAS  PubMed  Google Scholar 

  • Nelson JB, Hedican SP, George DJ et al (1995) Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med 1: 944–949

    Article  CAS  PubMed  Google Scholar 

  • O’Brien CA, Gubrij I, Lin SC et al (1999) STAT3 activation in stromal/osteoblastic cells is required for induction of the receptor activator of NF-kappaB ligand and stimulation of osteoclastogenesis by gp130-utilizing cytokines or interleukin-1 but not 1,25-dihydroxyvitamin D3 or parathyroid hormone. J Biol Chem 274: 19301–19308

    Article  PubMed  Google Scholar 

  • Paget S (1889) The distribution of secondary growths in cancer of the breast. Lancet 8: 98–101

    Google Scholar 

  • Powell GJ, Southby J, Danks JA et al (1991) Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res 51: 3059–3061

    CAS  PubMed  Google Scholar 

  • Rachner TD, Khosla S, Hofbauer LC (2011) Osteoporosis: now and the future. Lancet 377: 1276–1287

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rachner TD, Hadji P, Hofbauer LC (2012) Novel therapies in benign and malignant bone diseases. Pharmacol Ther 134: 338–344

    Article  CAS  PubMed  Google Scholar 

  • Roodman GD (2004) Mechanisms of bone metastasis. N Engl J Med 350: 1655–1664

    Article  CAS  PubMed  Google Scholar 

  • Rubin J, Chung LW, Fan X et al (2004) Prostate carcinoma cells that have resided in bone have an upregulated IGF-I axis. Prostate 58: 41–49

    Article  CAS  PubMed  Google Scholar 

  • Schramek D, Leibbrandt A, Sigl V et al (2010) Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer. Nature 468: 98–102

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Simonet WS, Lacey DL, Dunstan CR et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89: 309–319

    Article  CAS  PubMed  Google Scholar 

  • Smith MR, Saad F, Coleman R et al (2012) Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet 379: 39–46

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sotiriou C, Lacroix M, Lespagnard L et al (2001) Interleukins-6 and -11 expression in primary breast cancer and subsequent development of bone metastases. Cancer Lett 169: 87–95

    Article  CAS  PubMed  Google Scholar 

  • Southby J, Kissin MW, Danks JA et al (1990) Immunohistochemical localization of parathyroid hormone-related protein in human breast cancer. Cancer Res 50: 7710–7716

    CAS  PubMed  Google Scholar 

  • Tian E, Zhan F, Walker R et al (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349: 2483–2494

    Article  CAS  PubMed  Google Scholar 

  • Van Poznak C, Cross SS, Saggese M et al (2006) Expression of osteoprotegerin (OPG), TNF related apoptosis inducing ligand (TRAIL), and receptor activator of nuclear factor kappaB ligand (RANKL) in human breast tumours. J Clin Pathol 59: 56–63

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Virk MS, Alaee F, Petrigliano FA et al (2011) Combined inhibition of the BMP pathway and the RANK-RANKL axis in a mixed lytic/blastic prostate cancer lesion. Bone 48: 578–587

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Voorzanger-Rousselot N, Goehrig D, Journe F et al (2007) Increased Dickkopf-1 expression in breast cancer bone metastases. Br J Cancer 97: 964–970

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xiong J, Onal M, Jilka RL et al (2011) Matrix-embedded cells control osteoclast formation. Nat Med 17: 1235–1241

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yin JJ, Mohammad KS, Käkönen SM et al (2003) A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. Proc Natl Acad Sci USA 100: 10954–10959

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Medizinische Klinik III, Bereich Endokrinologie, Universitätsklinikum Carl Gustav Carus Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland

    Tilman D. Rachner & Lorenz C. Hofbauer

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  1. Tilman D. Rachner
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  2. Lorenz C. Hofbauer
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Correspondence to Tilman D. Rachner .

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Editors and Affiliations

  1. Universitätsklinik für Urologie, Universitätsklinikum Tübingen, Tübingen, Germany

    Arnulf Stenzl

  2. Universitätsfrauenklinik Düsseldorf, Düsseldorf, Germany

    Tanja Fehm

  3. Medizinische Klinik III, Bereich Endokrinologie, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany

    Lorenz C. Hofbauer

  4. Orthopädisches Zentrum für Muskuloskelettale Forschung, Universität Würzburg, Würzburg, Germany

    Franz Jakob

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Rachner, T., Hofbauer, L. (2014). Interaktion von Tumorzellen und Knochen bei osteolytischen/osteosklerotischen Metastasen, Circulus vitiosus der Knochenmetastasierung. In: Stenzl, A., Fehm, T., Hofbauer, L., Jakob, F. (eds) Knochenmetastasen. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-43471-0_2

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  • DOI: https://doi.org/10.1007/978-3-662-43471-0_2

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  • Print ISBN: 978-3-662-43470-3

  • Online ISBN: 978-3-662-43471-0

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