Bone Tropism in Cancer Metastases.

Bone is a frequent site of metastases in many cancers. Both bone properties and the tumor-intrinsic traits are associated with the metastatic propensity to bone (i.e., the bone tropism). Whereas an increasing body of mechanistic studies expanded our understanding on bone tropism, they also revealed complexity across the bone lesions originated from different cancer types. In this review, we will discuss the physical, chemical, and biological properties of bone microenvironment, identify potential players in every stage of bone metastases, and introduce some of the known mechanisms regulating the bone colonization. Our objectives are to integrate the knowledge established in different biological contexts and highlight the determinants of bone tropism.

[1]  Yibin Kang,et al.  Bone Vascular Niche E-selectin Induces Mesenchymal-Epithelial Transition and Wnt Activation in Cancer Cells to Promote Bone Metastasis , 2019, Nature Cell Biology.

[2]  Libing Song,et al.  Wnt5a induces and maintains prostate cancer cells dormancy in bone , 2018, The Journal of experimental medicine.

[3]  X. Zhang,et al.  Bone Metastasis: Find Your Niche and Fit in. , 2019, Trends in cancer.

[4]  Stephen T. C. Wong,et al.  The Osteogenic Niche Is a Calcium Reservoir of Bone Micrometastases and Confers Unexpected Therapeutic Vulnerability. , 2018, Cancer cell.

[5]  A. Dingemans,et al.  Association of molecular status and metastatic organs at diagnosis in patients with stage IV non-squamous non-small cell lung cancer. , 2018, Lung cancer.

[6]  Yibin Kang,et al.  The Biology of Bone Metastasis. , 2018, Cold Spring Harbor perspectives in medicine.

[7]  T. Voet,et al.  Identification of the tumour transition states occurring during EMT , 2018, Nature.

[8]  J. Blenis,et al.  Unique Metabolic Adaptations Dictate Distal Organ-Specific Metastatic Colonization. , 2018, Cancer cell.

[9]  I. Moskalev,et al.  Calcium-sensing receptor (CaSR) promotes development of bone metastasis in renal cell carcinoma , 2018, Oncotarget.

[10]  Gustav Stålhammar,et al.  Evolutionary history of metastatic breast cancer reveals minimal seeding from axillary lymph nodes , 2018, The Journal of clinical investigation.

[11]  N. Kosaka,et al.  Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A , 2018, Proceedings of the National Academy of Sciences.

[12]  L. Suva,et al.  Hallmarks of Bone Metastasis , 2018, Calcified Tissue International.

[13]  R. Gomis,et al.  MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer , 2018, Nature Cell Biology.

[14]  R. Gillies,et al.  MDA-MB-231 breast cancer cells fuel osteoclast metabolism and activity: A new rationale for the pathogenesis of osteolytic bone metastases. , 2017, Biochimica et biophysica acta. Molecular basis of disease.

[15]  Omar K. Yaghi,et al.  Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neutrophils , 2017, Science.

[16]  K. Pienta,et al.  Tenascin-C and Integrin α9 Mediate Interactions of Prostate Cancer with the Bone Microenvironment. , 2017, Cancer research.

[17]  J. Wang,et al.  Exosomal miR-141-3p regulates osteoblast activity to promote the osteoblastic metastasis of prostate cancer , 2017, Oncotarget.

[18]  Shuiping Gao,et al.  Comparison of patterns and prognosis among distant metastatic breast cancer patients by age groups: a SEER population-based analysis , 2017, Scientific Reports.

[19]  Courtney M. Karner,et al.  Glucose metabolism in bone. , 2017, Bone.

[20]  A. Giaccia,et al.  Hypoxia and Bone Metastatic Disease , 2017, Current Osteoporosis Reports.

[21]  Xiaoping Zhou,et al.  Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer. , 2017, Developmental cell.

[22]  S. Hung,et al.  Role of estrogen receptors and Src signaling in mechanisms of bone metastasis by estrogen receptor positive breast cancers , 2017, Journal of Translational Medicine.

[23]  Stephen T. C. Wong,et al.  Bone-in-culture array as a platform to model early-stage bone metastases and discover anti-metastasis therapies , 2017, Nature Communications.

[24]  B. Vincenzi,et al.  Determinants of bone specific metastasis in prostate cancer. , 2017, Critical reviews in oncology/hematology.

[25]  Thomas R. Cox,et al.  Pre-metastatic niches: organ-specific homes for metastases , 2017, Nature Reviews Cancer.

[26]  Nuno Bonito,et al.  Bone Metastases: An Overview , 2017, Oncology reviews.

[27]  A. Welm,et al.  RON kinase: A target for treatment of cancer-induced bone destruction and osteoporosis , 2017, Science Translational Medicine.

[28]  M. Brevet,et al.  Lysyl Oxidase Is a Strong Determinant of Tumor Cell Colonization in Bone. , 2016, Cancer research.

[29]  Daniele M. Gilkes Implications of Hypoxia in Breast Cancer Metastasis to Bone , 2016, International journal of molecular sciences.

[30]  Joshua R. Johnson,et al.  Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow , 2016, Nature Cell Biology.

[31]  C. McCall,et al.  Dormant breast cancer micrometastases reside in specific bone marrow niches that regulate their transit to and from bone , 2016, Science Translational Medicine.

[32]  Charles Swanton,et al.  Metastasis as an evolutionary process , 2016, Science.

[33]  Elisa de Stanchina,et al.  Metastatic Latency and Immune Evasion through Autocrine Inhibition of WNT , 2016, Cell.

[34]  Y. Shiozawa,et al.  Mouse models for studying prostate cancer bone metastasis. , 2016, BoneKEy reports.

[35]  Yibin Kang,et al.  Probing the Fifty Shades of EMT in Metastasis. , 2016, Trends in cancer.

[36]  C Tristan Stayton,et al.  What does convergent evolution mean? The interpretation of convergence and its implications in the search for limits to evolution , 2015, Interface Focus.

[37]  Gary K. Schwartz,et al.  Tumour exosome integrins determine organotropic metastasis , 2015, Nature.

[38]  Wenjun Xie,et al.  Excess TGF-β mediates muscle weakness associated with bone metastases in mice , 2015, Nature Medicine.

[39]  R. Govindan,et al.  Bone metastases in lung cancer. Potential novel approaches to therapy. , 2015, American journal of respiratory and critical care medicine.

[40]  Likun Chen,et al.  Osteopontin is a useful predictor of bone metastasis and survival in patients with locally advanced nasopharyngeal carcinoma , 2015, International journal of cancer.

[41]  G. Carmeliet,et al.  The vasculature: a vessel for bone metastasis. , 2015, BoneKEy reports.

[42]  J. Massagué,et al.  Surviving at a Distance: Organ-Specific Metastasis. , 2015, Trends in cancer.

[43]  R. Linding,et al.  The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase , 2015, Nature.

[44]  M. Kerin,et al.  Metastatic breast cancer: the potential of miRNA for diagnosis and treatment monitoring , 2015, Cancer and Metastasis Reviews.

[45]  Stephen T. C. Wong,et al.  The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells. , 2015, Cancer cell.

[46]  G. Semenza,et al.  Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells , 2014, Proceedings of the National Academy of Sciences.

[47]  M. Kennedy,et al.  Osteopontin-a alters glucose homeostasis in anchorage-independent breast cancer cells. , 2014, Cancer letters.

[48]  K. Junker,et al.  High calcium concentration in bones promotes bone metastasis in renal cell carcinomas expressing calcium-sensing receptor , 2014, Molecular Cancer.

[49]  J. Charles,et al.  Bone and the Innate Immune System , 2014, Current Osteoporosis Reports.

[50]  F. de Marinis,et al.  Bone and brain metastasis in lung cancer: recent advances in therapeutic strategies , 2014, Therapeutic advances in medical oncology.

[51]  A. Godwin,et al.  Bone sialoprotein and osteopontin in bone metastasis of osteotropic cancers. , 2014, Critical reviews in oncology/hematology.

[52]  D. Amadori,et al.  Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic bone metastasis. , 2013, Cancer cell.

[53]  J. Foekens,et al.  Selection of Bone Metastasis Seeds by Mesenchymal Signals in the Primary Tumor Stroma , 2013, Cell.

[54]  Mina J. Bissell,et al.  The perivascular niche regulates breast tumor dormancy , 2013, Nature Cell Biology.

[55]  Yibin Kang,et al.  Tumor cell dissemination: emerging biological insights from animal models and cancer patients. , 2013, Cancer cell.

[56]  E. Thompson,et al.  Cancer: The to and fro of tumour spread , 2013, Nature.

[57]  G. Siegal,et al.  Depletion of Plasmacytoid Dendritic Cells Inhibits Tumor Growth and Prevents Bone Metastasis of Breast Cancer Cells , 2012, The Journal of Immunology.

[58]  S. Narod Tumour size predicts long-term survival among women with lymph node-positive breast cancer. , 2012, Current oncology.

[59]  U. Schumacher,et al.  Selectin-deficiency reduces the number of spontaneous metastases in a xenograft model of human breast cancer. , 2012, Cancer letters.

[60]  Paul J Hertzog,et al.  Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape , 2012, Nature Medicine.

[61]  K. Pienta,et al.  Cyclophosphamide creates a receptive microenvironment for prostate cancer skeletal metastasis. , 2012, Cancer research.

[62]  G van der Pluijm,et al.  The BMP2/7 heterodimer inhibits the human breast cancer stem cell subpopulation and bone metastases formation , 2012, Oncogene.

[63]  M. Watabe,et al.  Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone , 2012, Journal of Experimental Medicine.

[64]  L. Tran,et al.  Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells. , 2012, Cancer research.

[65]  J. Massagué,et al.  VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors. , 2011, Cancer cell.

[66]  N. Ridgway,et al.  Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. , 2011, Journal of thoracic disease.

[67]  Huanbin Xu,et al.  Bone marrow and the control of immunity , 2011, Cellular and Molecular Immunology.

[68]  Robert A. Weinberg,et al.  Tumor Metastasis: Molecular Insights and Evolving Paradigms , 2011, Cell.

[69]  F. Prinz,et al.  Believe it or not: how much can we rely on published data on potential drug targets? , 2011, Nature Reviews Drug Discovery.

[70]  Charles P. Lin,et al.  In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche , 2011, Nature.

[71]  T. Guise,et al.  Cancer to bone: a fatal attraction , 2011, Nature Reviews Cancer.

[72]  J. Waxman,et al.  Bone metastasis in prostate cancer: emerging therapeutic strategies , 2011, Nature Reviews Clinical Oncology.

[73]  K. Pienta,et al.  Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. , 2011, The Journal of clinical investigation.

[74]  Charity L. Washam,et al.  Bone metastasis: mechanisms and therapeutic opportunities , 2011, Nature Reviews Endocrinology.

[75]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[76]  Yibin Kang,et al.  Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. , 2011, Cancer cell.

[77]  K. Hoek,et al.  GLI2-mediated melanoma invasion and metastasis. , 2010, Journal of the National Cancer Institute.

[78]  Karen Gelmon,et al.  Metastatic behavior of breast cancer subtypes. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[79]  Beverly A. Teicher,et al.  CXCL12 (SDF-1)/CXCR4 Pathway in Cancer , 2010, Clinical Cancer Research.

[80]  B. Milleron,et al.  Osteoblastic Reaction in Non-small Cell Lung Carcinoma and its Association to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Response and Prolonged Survival , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[81]  Roman K. Thomas,et al.  Osteoblastic response in patients with non-small cell lung cancer with activating EGFR Mutations and bone metastases during treatment with EGFR kinase inhibitors. , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[82]  J. Chirgwin,et al.  Hypoxia and TGF-β Drive Breast Cancer Bone Metastases through Parallel Signaling Pathways in Tumor Cells and the Bone Microenvironment , 2009, PloS one.

[83]  Robert J Griffin,et al.  Mechanisms of bone metastases of breast cancer. , 2009, Endocrine-related cancer.

[84]  Jeffrey M. Rosen,et al.  Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features , 2009, Proceedings of the National Academy of Sciences.

[85]  Monica Morrow,et al.  Presenting Features of Breast Cancer Differ by Molecular Subtype , 2009, Annals of Surgical Oncology.

[86]  Larry Norton,et al.  Latent bone metastasis in breast cancer tied to Src-dependent survival signals. , 2009, Cancer cell.

[87]  Paula D. Bos,et al.  Metastasis: from dissemination to organ-specific colonization , 2009, Nature Reviews Cancer.

[88]  M. Kitajima,et al.  Clinical Significance of Circulating Tumor Cells in Blood from Patients with Gastrointestinal Cancers , 2008, Annals of Surgical Oncology.

[89]  C. Logothetis,et al.  Cadherin-11 Promotes the Metastasis of Prostate Cancer Cells to Bone , 2008, Molecular Cancer Research.

[90]  Wenjun Guo,et al.  The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells , 2008, Cell.

[91]  John W M Martens,et al.  Subtypes of breast cancer show preferential site of relapse. , 2008, Cancer research.

[92]  H. Broxmeyer Chemokines in hematopoiesis , 2008, Current opinion in hematology.

[93]  T. Yoneda,et al.  Hypoxia and hypoxia-inducible factor-1 expression enhance osteolytic bone metastases of breast cancer. , 2007, Cancer research.

[94]  D. Scadden,et al.  Therapeutic targeting of a stem cell niche , 2007, Nature Biotechnology.

[95]  R. Coleman Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity , 2006, Clinical Cancer Research.

[96]  J. Chirgwin,et al.  Basic Mechanisms Responsible for Osteolytic and Osteoblastic Bone Metastases , 2006, Clinical Cancer Research.

[97]  A. Giuliano,et al.  Most Early Disseminated Cancer Cells Detected in Bone Marrow of Breast Cancer Patients Have a Putative Breast Cancer Stem Cell Phenotype , 2006, Clinical Cancer Research.

[98]  A. Schneider,et al.  Extracellular calcium as a candidate mediator of prostate cancer skeletal metastasis. , 2006, Cancer research.

[99]  K. Miura,et al.  Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression , 2006, Nature Medicine.

[100]  J. Chirgwin,et al.  Does Prostate-Specific Antigen Contribute to Bone Metastases? , 2006, Clinical Cancer Research.

[101]  G. Scagliotti,et al.  Management of bone metastases in cancer: a review. , 2005, Critical reviews in oncology/hematology.

[102]  W. Gerald,et al.  Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. , 2005, The Journal of clinical investigation.

[103]  J. Chirgwin,et al.  A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[104]  Paul J. Williams,et al.  C-SRC tyrosine kinase activity is associated with tumor colonization in bone and lung in an animal model of human breast cancer metastasis. , 2003, Cancer research.

[105]  C. Cordon-Cardo,et al.  A multigenic program mediating breast cancer metastasis to bone. , 2003, Cancer cell.

[106]  G. Mundy Metastasis: Metastasis to bone: causes, consequences and therapeutic opportunities , 2002, Nature Reviews Cancer.

[107]  Sandrine Bongiovanni,et al.  Transcriptional Program of Mouse Osteoclast Differentiation Governed by the Macrophage Colony-stimulating Factor and the Ligand for the Receptor Activator of NFκB* , 2002, The Journal of Biological Chemistry.

[108]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[109]  G. Bastert,et al.  Enrichment of memory T cells and other profound immunological changes in the bone marrow from untreated breast cancer patients , 2001, International journal of cancer.

[110]  T. Mcclanahan,et al.  Involvement of chemokine receptors in breast cancer metastasis , 2001, Nature.

[111]  E. Brown,et al.  Extracellular calcium-sensing receptor expression and its potential role in regulating parathyroid hormone-related peptide secretion in human breast cancer cell lines. , 2000, Endocrinology.

[112]  H. Moch,et al.  Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. , 2000, Human pathology.

[113]  H. Lilja,et al.  Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen. , 1996, Urology.

[114]  J. Nelson,et al.  Identification of endothelin–1 in the pathophysiology of metastatic adenocarcinoma of the prostate , 1995, Nature Medicine.

[115]  F. Jakob,et al.  A Subpopulation of Stromal Cells Controls Cancer Cell Homing to the Bone Marrow. , 2018, Cancer research.

[116]  D. Basanta,et al.  Current and emerging therapies for bone metastatic castration-resistant prostate cancer. , 2015, Cancer control : journal of the Moffitt Cancer Center.

[117]  T. Seyfried,et al.  On the origin of cancer metastasis. , 2013, Critical reviews in oncogenesis.

[118]  G. Andriole The impact of prostate cancer and hormonal therapy on bone. , 2009, Reviews in urology.

[119]  T. Giordano,et al.  NF-κB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF , 2007, Nature Medicine.

[120]  Daphne Vassiliou,et al.  Differential expression of osteopontin and bone sialoprotein in bone metastasis of breast and prostate carcinoma , 2004, Clinical & Experimental Metastasis.