Pre-metastatic niches: organ-specific homes for metastases

It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the 'seeds' of metastasis requires the action of tumour-secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche.

[1]  R. Donato,et al.  Functions of S100 proteins. , 2012, Current molecular medicine.

[2]  E. White,et al.  Fibronectin splice variants: Understanding their multiple roles in health and disease using engineered mouse models , 2011, IUBMB life.

[3]  S. Steinberg,et al.  Alterations in Pericyte Subpopulations Are Associated with Elevated Blood–Tumor Barrier Permeability in Experimental Brain Metastasis of Breast Cancer , 2016, Clinical Cancer Research.

[4]  K. Chan,et al.  Targeting VEGFR1- and VEGFR2-expressing non-tumor cells is essential for esophageal cancer therapy , 2014, Oncotarget.

[5]  Amber J. Giles,et al.  Activation of Hematopoietic Stem/Progenitor Cells Promotes Immunosuppression Within the Pre-metastatic Niche. , 2016, Cancer research.

[6]  M. Konopleva,et al.  The CXCR4 Antagonist AMD3465 Regulates Oncogenic Signaling and Invasiveness In Vitro and Prevents Breast Cancer Growth and Metastasis In Vivo , 2013, PloS one.

[7]  S. Pomeroy,et al.  Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. , 2011, Nature communications.

[8]  R. Hynes,et al.  Platelets guide the formation of early metastatic niches , 2014, Proceedings of the National Academy of Sciences.

[9]  H. Randeva,et al.  Obesity and prostate cancer: a role for adipokines. , 2007, European urology.

[10]  Zhiyuan Hu,et al.  Label-Free Quantitative Detection of Tumor-Derived Exosomes through Surface Plasmon Resonance Imaging , 2014, Analytical chemistry.

[11]  R. Jain Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy , 2005, Science.

[12]  G. Semenza,et al.  Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation , 2011, Proceedings of the National Academy of Sciences.

[13]  H. Saji,et al.  Significant correlation of monocyte chemoattractant protein‐1 expression with neovascularization and progression of breast carcinoma , 2001, Cancer.

[14]  M. Zöller,et al.  CD44v6 dependence of premetastatic niche preparation by exosomes. , 2009, Neoplasia.

[15]  J. Wolchok,et al.  Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation , 2015, Nature Communications.

[16]  E. Dejana,et al.  Inhibition of endothelial FAK activity prevents tumor metastasis by enhancing barrier function , 2014, The Journal of cell biology.

[17]  Qiongqing Wang,et al.  ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. , 2009, Genes & development.

[18]  Lei Zhao,et al.  Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice. , 2012, Blood.

[19]  C. Théry,et al.  Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. , 2014, Annual review of cell and developmental biology.

[20]  Matthew J. Craig,et al.  Targeting CCL2 with systemic delivery of neutralizing antibodies induces prostate cancer tumor regression in vivo. , 2007, Cancer research.

[21]  P. Black,et al.  Angiogenesis, Metastasis, and Endogenous Inhibition , 2000, Journal of Neuro-Oncology.

[22]  Gabriele Bergers,et al.  Modes of resistance to anti-angiogenic therapy , 2008, Nature Reviews Cancer.

[23]  P. Friedl,et al.  Tumour-cell invasion and migration: diversity and escape mechanisms , 2003, Nature Reviews Cancer.

[24]  C. Francis,et al.  Impact of venous thromboembolism and anticoagulation on cancer and cancer survival. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  Ricardo Garcia,et al.  Biomechanical Remodeling of the Microenvironment by Stromal Caveolin-1 Favors Tumor Invasion and Metastasis , 2011, Cell.

[26]  Hamid Cheshmi Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers , 2011 .

[27]  G. Semenza,et al.  Inhibitors of hypoxia-inducible factor 1 block breast cancer metastatic niche formation and lung metastasis , 2012, Journal of Molecular Medicine.

[28]  H. Moses,et al.  Gr-1+CD11b+ myeloid cells tip the balance of immune protection to tumor promotion in the premetastatic lung. , 2010, Cancer research.

[29]  Paula D. Bos,et al.  Mediators of vascular remodelling co-opted for sequential steps in lung metastasis , 2007, Nature.

[30]  M. Shibuya,et al.  MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. , 2002, Cancer cell.

[31]  S. Rafii,et al.  Incremental increase in VEGFR1+ hematopoietic progenitor cells and VEGFR2+ endothelial progenitor cells predicts relapse and lack of tumor response in breast cancer patients , 2012, Breast Cancer Research and Treatment.

[32]  R. Figlin,et al.  S1PR1-STAT3 signaling is crucial for myeloid cell colonization at future metastatic sites. , 2012, Cancer cell.

[33]  Menotti Ruvo,et al.  Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models , 2015, Oncotarget.

[34]  G. Mills,et al.  Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth , 2011, Nature Medicine.

[35]  Tomoyuki Shirai,et al.  MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. , 2005, Cancer cell.

[36]  Jinghang Zhang,et al.  CCL2 recruits inflammatory monocytes to facilitate breast tumor metastasis , 2011, Nature.

[37]  C. Klein,et al.  Parallel progression of primary tumours and metastases , 2009, Nature Reviews Cancer.

[38]  D. Lyden,et al.  The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts. , 2011, Seminars in cancer biology.

[39]  E. Messing,et al.  E-selectin ligand-1 controls circulating prostate cancer cell rolling/adhesion and metastasis , 2014, Oncotarget.

[40]  Z. Werb,et al.  Matrix Metalloproteinases: Regulators of the Tumor Microenvironment , 2010, Cell.

[41]  Weiying Zhou,et al.  Breast cancer-secreted miR-122 reprograms glucose metabolism in pre-metastatic niche to promote metastasis , 2015, Nature Cell Biology.

[42]  Wei He,et al.  Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[43]  S. Rafii,et al.  Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells , 2010, Nature Cell Biology.

[44]  V. Adamo,et al.  Prognostic impact of CD133 immunoexpression in node-negative invasive breast carcinomas. , 2011, Anticancer research.

[45]  Janet L Stein,et al.  Canonical WNT Signaling Promotes Osteogenesis by Directly Stimulating Runx2 Gene Expression* , 2005, Journal of Biological Chemistry.

[46]  Evan T. Keller,et al.  Type I collagen receptor (α2β1) signaling promotes prostate cancer invasion through RhoC GTPase , 2008 .

[47]  T. Fehm,et al.  Persistence of Disseminated Tumor Cells in the Bone Marrow of Breast Cancer Patients Predicts Increased Risk for Relapse—A European Pooled Analysis , 2011, Clinical Cancer Research.

[48]  Anna Janowska-Wieczorek,et al.  Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer , 2005, International journal of cancer.

[49]  Yu Zhang,et al.  Development and characterization of a reliable mouse model of colorectal cancer metastasis to the liver , 2013, Clinical & Experimental Metastasis.

[50]  G. Semenza,et al.  Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis , 2014, Proceedings of the National Academy of Sciences.

[51]  B F Boyce,et al.  Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis. , 1996, The Journal of clinical investigation.

[52]  R. Demicheli,et al.  Reduction of Breast Cancer Relapses with Perioperative Non-Steroidal Anti-Inflammatory Drugs: New Findings and a Review , 2013, Current medicinal chemistry.

[53]  E. Passegué,et al.  Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils , 2015, Proceedings of the National Academy of Sciences.

[54]  William C Hines,et al.  Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression , 2011, Nature Medicine.

[55]  Graça Raposo,et al.  Extracellular vesicles: Exosomes, microvesicles, and friends , 2013, The Journal of cell biology.

[56]  G. Merlino,et al.  The Two Faces of Interferon-γ in Cancer , 2011, Clinical Cancer Research.

[57]  Yan-xia Lu,et al.  Human CD133-positive hematopoietic progenitor cells initiate growth and metastasis of colorectal cancer cells. , 2014, Carcinogenesis.

[58]  Yi Lu,et al.  Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. , 2005, Cancer research.

[59]  J. Pollard,et al.  Microenvironmental regulation of metastasis , 2009, Nature Reviews Cancer.

[60]  Adam J Engler,et al.  Multiscale Modeling of Form and Function , 2009, Science.

[61]  A. Kudo Periostin in fibrillogenesis for tissue regeneration: periostin actions inside and outside the cell , 2011, Cellular and Molecular Life Sciences.

[62]  K. Camphausen,et al.  Brain metastases as preventive and therapeutic targets , 2011, Nature Reviews Cancer.

[63]  J. Sleeman,et al.  The metastatic niche and stromal progression , 2012, Cancer and Metastasis Reviews.

[64]  Quynh-Thu Le,et al.  Lysyl oxidase is essential for hypoxia-induced metastasis , 2006, Nature.

[65]  M. Headley,et al.  Visualization of immediate immune responses to pioneer metastatic cells in the lung , 2016, Nature.

[66]  P. Bragado,et al.  TGFβ2 dictates disseminated tumour cell fate in target organs through TGFβ-RIII and p38α/β signalling , 2013, Nature Cell Biology.

[67]  Xin Lu,et al.  Organotropism of Breast Cancer Metastasis , 2007, Journal of Mammary Gland Biology and Neoplasia.

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

[69]  J. Erler,et al.  Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. , 2009, Cancer cell.

[70]  P. V. van Diest,et al.  Ischemia/reperfusion accelerates the outgrowth of hepatic micrometastases in a highly standardized murine model , 2005, Hepatology.

[71]  J. Schneider,et al.  Integrins and bone metastasis: integrating tumor cell and stromal cell interactions. , 2011, Bone.

[72]  Li-Xin Wei,et al.  Inhibition of tumor necrosis factor alpha reduces the outgrowth of hepatic micrometastasis of colorectal tumors in a mouse model of liver ischemia-reperfusion injury , 2014, Journal of Biomedical Science.

[73]  Thomas R Cox,et al.  LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis. , 2013, Cancer research.

[74]  Shigeyoshi Itohara,et al.  Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis , 2000, Nature Cell Biology.

[75]  S. Diaz-Cano Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design , 2012, International journal of molecular sciences.

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

[77]  Robert A. Weinberg,et al.  Metastatic colonization: settlement, adaptation and propagation of tumor cells in a foreign tissue environment. , 2011, Seminars in cancer biology.

[78]  J. Herndon,et al.  T1 lung cancers: sensitivity of diagnosis with fluorodeoxyglucose PET. , 2002, Radiology.

[79]  Wan-Wan Lin,et al.  Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis , 2009, Nature.

[80]  Thijs J. Hagenbeek,et al.  Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes , 2010, Proceedings of the National Academy of Sciences.

[81]  T. Martin,et al.  Breast Cancer Cells Interact with Osteoblasts to Support Osteoclast Formation* , 2022 .

[82]  Hua Yu,et al.  CD8+ T‐cell immunosurveillance constrains lymphoid premetastatic myeloid cell accumulation , 2015, European journal of immunology.

[83]  G. Nicolson,et al.  Organ selectivity for implantation survival and growth of B16 melanoma variant tumor lines. , 1976, Journal of the National Cancer Institute.

[84]  Thomas R. Cox,et al.  Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer , 2011, Disease Models & Mechanisms.

[85]  F. Klawonn,et al.  The lack of type I interferon induces neutrophil‐mediated pre‐metastatic niche formation in the mouse lung , 2015, International journal of cancer.

[86]  K. Chang,et al.  P2Y2R activation by nucleotides released from the highly metastatic breast cancer cell contributes to pre-metastatic niche formation by mediating lysyl oxidase secretion, collagen crosslinking, and monocyte recruitment , 2014, Oncotarget.

[87]  Mikala Egeblad,et al.  Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling , 2009, Cell.

[88]  Samuel A Wickline,et al.  Magnetic resonance imaging of melanoma exosomes in lymph nodes , 2015, Magnetic resonance in medicine.

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

[90]  Carolyn J. Anderson,et al.  Very Late Antigen-4 (α4β1 Integrin) Targeted PET Imaging of Multiple Myeloma , 2013, PloS one.

[91]  T. Ørntoft,et al.  Cellular disposal of miR23b by RAB27-dependent exosome release is linked to acquisition of metastatic properties. , 2014, Cancer research.

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

[93]  I. Fidler,et al.  Role of organ selectivity in the determination of metastatic patterns of B16 melanoma. , 1980, Cancer research.

[94]  Paul J. Williams,et al.  Anti-alpha4 integrin antibody suppresses the development of multiple myeloma and associated osteoclastic osteolysis. , 2004, Blood.

[95]  G. Ouyang,et al.  Periostin promotes immunosuppressive premetastatic niche formation to facilitate breast tumour metastasis , 2016, The Journal of pathology.

[96]  C. Lopes,et al.  Tumor Cell-educated Periprostatic Adipose Tissue Acquires an Aggressive Cancer-promoting Secretory Profile , 2012, Cellular Physiology and Biochemistry.

[97]  L. Norton,et al.  Tumor entrained neutrophils inhibit seeding in the premetastatic lung. , 2011, Cancer cell.

[98]  M. C. Hollander,et al.  Platelet factor 4 is produced by subsets of myeloid cells in premetastatic lung and inhibits tumor metastasis , 2016, Oncotarget.

[99]  I. Malanchi,et al.  Neutrophils support lung colonization of metastasis-initiating breast cancer cells , 2015, Nature.

[100]  Ruth J. Muschel,et al.  Coagulation Facilitates Tumor Cell Spreading in the Pulmonary Vasculature during Early Metastatic Colony Formation , 2004, Cancer Research.

[101]  S. Wickline,et al.  Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. , 2011, Cancer research.

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

[103]  D. Quail,et al.  Microenvironmental regulation of tumor progression and metastasis , 2014 .

[104]  Andrew R. Chin,et al.  Cancer Tills the Premetastatic Field: Mechanistic Basis and Clinical Implications , 2016, Clinical Cancer Research.

[105]  Larissa V Furtado,et al.  Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? A report of the association for molecular pathology. , 2015, The Journal of molecular diagnostics : JMD.

[106]  Qinghua Zhou,et al.  Monocyte chemotactic protein 1 promotes lung cancer-induced bone resorptive lesions in vivo. , 2009, Neoplasia.

[107]  J. Lötvall,et al.  Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells , 2007, Nature Cell Biology.

[108]  Roger R. Gomis,et al.  TGFβ Primes Breast Tumors for Lung Metastasis Seeding through Angiopoietin-like 4 , 2008, Cell.

[109]  F. Sánchez‐Madrid,et al.  Sorting it out: regulation of exosome loading. , 2014, Seminars in cancer biology.

[110]  S Paget,et al.  THE DISTRIBUTION OF SECONDARY GROWTHS IN CANCER OF THE BREAST. , 1889 .

[111]  Xuetao Cao,et al.  Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils. , 2016, Cancer cell.

[112]  A. Guimarães,et al.  A high HIF-1α expression genotype is associated with poor prognosis of upper aerodigestive tract carcinoma patients. , 2012, Oral oncology.

[113]  Hiroyuki Aburatani,et al.  Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis , 2006, Nature Cell Biology.

[114]  James Ewing,et al.  Neoplastic Diseases: A Treatise on Tumours , 1928, The Indian Medical Gazette.

[115]  A. Guha,et al.  Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells , 2008, Nature Cell Biology.

[116]  H. Saya,et al.  Periostin Is a Key Niche Component for Wound Metastasis of Melanoma , 2015, PloS one.

[117]  W. Moses Fundamental Limits of Spatial Resolution in PET. , 2011, Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment.

[118]  T. Guise Examining the metastatic niche: targeting the microenvironment. , 2010, Seminars in oncology.

[119]  J. Sleeman,et al.  A link between inflammation and metastasis: serum amyloid A1 and A3 induce metastasis, and are targets of metastasis-inducing S100A4 , 2014, Oncogene.

[120]  Hong Peng,et al.  Interactions between cancer stem cells and their niche govern metastatic colonization , 2011, Nature.

[121]  Andy J. Minn,et al.  Genes that mediate breast cancer metastasis to lung , 2005, Nature.

[122]  Gema Moreno-Bueno,et al.  Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET , 2012, Nature Medicine.

[123]  Sharad K Sharma,et al.  Pulmonary Alveolar Macrophages Contribute to the Premetastatic Niche by Suppressing Antitumor T Cell Responses in the Lungs , 2015, The Journal of Immunology.

[124]  K. Alitalo,et al.  VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. , 2007, Blood.

[125]  S. Rafii,et al.  VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche , 2005, Nature.

[126]  Jacopo Meldolesi,et al.  Shedding microvesicles: artefacts no more. , 2009, Trends in cell biology.

[127]  I. B. Borel Rinkes,et al.  Hypoxia After Liver Surgery Imposes an Aggressive Cancer Stem Cell Phenotype on Residual Tumor Cells , 2014, Annals of surgery.

[128]  A. Carracedo,et al.  Vesicle-MaNiA: extracellular vesicles in liquid biopsy and cancer. , 2016, Current opinion in pharmacology.

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

[130]  E. Edelman,et al.  Dysfunctional endothelial cells directly stimulate cancer inflammation and metastasis , 2013, International journal of cancer.

[131]  M. Watabe,et al.  Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone , 2011, The Journal of experimental medicine.

[132]  Christian Pilarsky,et al.  Glypican-1 identifies cancer exosomes and detects early pancreatic cancer , 2015, Nature.

[133]  Y. Meng,et al.  G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models , 2009, Proceedings of the National Academy of Sciences.

[134]  Z. Werb,et al.  New functions for the matrix metalloproteinases in cancer progression , 2002, Nature Reviews Cancer.

[135]  N. Sugimoto,et al.  High lung-metastatic variant of human osteosarcoma cells, selected by passage of lung metastasis in nude mice, is associated with increased expression of α(v)β(3) integrin. , 2013, Anticancer research.

[136]  D. Scadden Nice Neighborhood: Emerging Concepts of the Stem Cell Niche , 2014, Cell.

[137]  A. Brivanlou,et al.  The BMP Inhibitor Coco Reactivates Breast Cancer Cells at Lung Metastatic Sites , 2012, Cell.

[138]  J. Monboisse,et al.  Regulation of Tumor Cell Chemotaxis by Type IV Collagen Is Mediated by a Ca2+-dependent Mechanism Requiring CD47 and the Integrin αVβ3 * , 2000, The Journal of Biological Chemistry.

[139]  P. Ordóñez-Morán,et al.  Complex metastatic niches: already a target for therapy? , 2014, Current opinion in cell biology.

[140]  J. Sleeman,et al.  Building the niche: the role of the S100 proteins in metastatic growth. , 2012, Seminars in cancer biology.

[141]  G. Naumov,et al.  Persistence of solitary mammary carcinoma cells in a secondary site: a possible contributor to dormancy. , 2002, Cancer research.

[142]  A. Krüger,et al.  Tissue inhibitor of metalloproteinases (TIMP)‐1 creates a premetastatic niche in the liver through SDF‐1/CXCR4‐dependent neutrophil recruitment in mice , 2015, Hepatology.

[143]  A. Shiotani,et al.  Primary Tumor-Secreted Lymphangiogenic Factors Induce Pre-Metastatic Lymphvascular Niche Formation at Sentinel Lymph Nodes in Oral Squamous Cell Carcinoma , 2015, PloS one.

[144]  Satoshi Hirakawa,et al.  VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis , 2005, The Journal of experimental medicine.

[145]  Hubing Shi,et al.  Pulmonary vascular destabilization in the premetastatic phase facilitates lung metastasis. , 2009, Cancer research.

[146]  David J Weber,et al.  S100 proteins in cancer , 2015, Nature Reviews Cancer.

[147]  J Ratajczak,et al.  Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication , 2006, Leukemia.

[148]  G. Camussi,et al.  Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche. , 2011, Cancer research.

[149]  D. Galson,et al.  Monocyte chemotactic protein‐1 (MCP‐1) acts as a paracrine and autocrine factor for prostate cancer growth and invasion , 2006, The Prostate.

[150]  K. Mimori,et al.  Identification of the high-risk group for metastasis of gastric cancer cases by vascular endothelial growth factor receptor-1 overexpression in peripheral blood , 2007, British Journal of Cancer.

[151]  D. Bowtell,et al.  Primary tumor hypoxia recruits CD11b+/Ly6Cmed/Ly6G+ immune suppressor cells and compromises NK cell cytotoxicity in the premetastatic niche. , 2012, Cancer research.

[152]  S. Groshen,et al.  Interleukin-6 in the bone marrow microenvironment promotes the growth and survival of neuroblastoma cells. , 2009, Cancer research.

[153]  Cyrus M. Ghajar Metastasis prevention by targeting the dormant niche , 2015, Nature Reviews Cancer.

[154]  R. Jain,et al.  Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regulation , 2011, Proceedings of the National Academy of Sciences.

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

[156]  Michael A. Hollingsworth,et al.  Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver , 2015, Nature Cell Biology.

[157]  J. Serody,et al.  C-C chemokine receptor 5 on pulmonary fibrocytes facilitates migration and promotes metastasis via matrix metalloproteinase 9. , 2008, The American journal of pathology.

[158]  M. Ratajczak,et al.  Enhancing effect of platelet‐derived microvesicles on the invasive potential of breast cancer cells , 2006, Transfusion.

[159]  F. Keleştimur,et al.  VEGFR1 expression is related to lymph node metastasis and serum VEGF may be a marker of progression in the follow-up of patients with differentiated thyroid carcinoma. , 2011, European journal of endocrinology.

[160]  L. Hefler,et al.  Monocyte Chemoattractant Protein-1 Serum Levels in Patients with Breast Cancer , 2004, Tumor Biology.

[161]  J. D. Cameron,et al.  Type IV collagen and corneal epithelial adhesion and migration. Effects of type IV collagen fragments and synthetic peptides on rabbit corneal epithelial cell adhesion and migration in vitro. , 1991, Investigative ophthalmology & visual science.

[162]  Y. Fujiwara,et al.  Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone , 2015, Clinical & Experimental Metastasis.

[163]  J. Quillard,et al.  Enhanced expression of interleukin-6 in bone and serum of metastatic renal cell carcinoma. , 1998, Human pathology.

[164]  G. Parmiani,et al.  Tumour-released exosomes and their implications in cancer immunity , 2008, Cell Death and Differentiation.

[165]  S. Rafii,et al.  Myeloid progenitor cells in the premetastatic lung promote metastases by inducing mesenchymal to epithelial transition. , 2012, Cancer research.

[166]  M. Michael,et al.  Hypoxic enhancement of exosome release by breast cancer cells , 2012, BMC Cancer.

[167]  G. Raposo,et al.  As we wait: coping with an imperfect nomenclature for extracellular vesicles , 2013, Journal of extracellular vesicles.

[168]  A. Di Giannatale,et al.  The New Deal: A Potential Role for Secreted Vesicles in Innate Immunity and Tumor Progression , 2015, Front. Immunol..

[169]  J. Izbicki,et al.  Molecular Changes in Pre-Metastatic Lymph Nodes of Esophageal Cancer Patients , 2014, PloS one.

[170]  K. Lam,et al.  Molecular Imaging of Very Late Antigen–4 (α4β1 Integrin) in the Premetastatic Niche , 2012, The Journal of Nuclear Medicine.

[171]  F. Domann,et al.  Integrin α3β1 Can Function to Promote Spontaneous Metastasis and Lung Colonization of Invasive Breast Carcinoma , 2013, Molecular Cancer Research.

[172]  K. Pienta,et al.  Identification of leukocyte E-selectin ligands, P-selectin glycoprotein ligand-1 and E-selectin ligand-1, on human metastatic prostate tumor cells. , 2005, Cancer research.

[173]  R. Jove,et al.  Prognostic Significance of Neutrophilic Infiltration in Benign Lymph Nodes in Patients with Muscle-invasive Bladder Cancer. , 2017, European urology focus.

[174]  J Ratajczak,et al.  Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery , 2006, Leukemia.

[175]  B. Lévy,et al.  Hepatic ischemia-reperfusion increases circulating bone marrow-derived progenitor cells and tumor growth in a mouse model of colorectal liver metastases. , 2013, The Journal of surgical research.

[176]  Weiying Zhou,et al.  Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. , 2014, Cancer cell.

[177]  Bethan Psaila,et al.  The metastatic niche: adapting the foreign soil , 2009, Nature Reviews Cancer.

[178]  D. Tarin,et al.  Dormant cancer cells retrieved from metastasis-free organs regain tumorigenic and metastatic potency. , 2006, The American journal of pathology.

[179]  R. Figlin,et al.  Targeted therapies: Pazopanib: carving a niche in a crowded therapeutic landscape , 2010, Nature Reviews Clinical Oncology.

[180]  M. Bissell,et al.  Breast cancer by proxy: can the microenvironment be both the cause and consequence? , 2009, Trends in molecular medicine.

[181]  W. Gerald,et al.  Genes that mediate breast cancer metastasis to the brain , 2009, Nature.

[182]  R. Kannagi,et al.  Induction of E-selectin expression on vascular endothelium by digestive system cancer cells , 1996, Journal of Gastroenterology.

[183]  R. Hynes,et al.  Lymphatic or Hematogenous Dissemination: How Does a Metastatic Tumor Cell Decide? , 2006, Cell cycle.

[184]  H. Aburatani,et al.  Primary tumours modulate innate immune signalling to create pre-metastatic vascular hyperpermeability foci , 2013, Nature Communications.

[185]  P. Steeg,et al.  Targeting metastasis , 2016, Nature Reviews Cancer.

[186]  Liz Y. Han,et al.  Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma , 2006, Nature Medicine.

[187]  K. Csiszȧr,et al.  Lysyl oxidase-like 2 (LOXL2) and E47 EMT factor: novel partners in E-cadherin repression and early metastasis colonization , 2014, Oncogene.

[188]  M. Christian,et al.  Measuring response in solid tumors: unidimensional versus bidimensional measurement. , 1999, Journal of the National Cancer Institute.

[189]  J. Sleeman The lymph node pre-metastatic niche , 2015, Journal of Molecular Medicine.

[190]  W. Hahn,et al.  Analysis of tumor- and stroma-supplied proteolytic networks reveals a brain metastasis-promoting role for cathepsin S , 2014, Nature Cell Biology.

[191]  Laurie J. Gay,et al.  Contribution of platelets to tumour metastasis , 2011, Nature Reviews Cancer.

[192]  M. Krieg,et al.  Tensile forces govern germ-layer organization in zebrafish , 2008, Nature Cell Biology.

[193]  J. Baillargeon,et al.  Obesity, adipokines, and prostate cancer (review). , 2006, International journal of oncology.

[194]  R. Figlin,et al.  Myeloid Clusters Are Associated with a Pro-Metastatic Environment and Poor Prognosis in Smoking-Related Early Stage Non-Small Cell Lung Cancer , 2013, PloS one.

[195]  G. Ahn,et al.  Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells. , 2008, Cancer cell.

[196]  Luzhe Sun,et al.  Protein tyrosine phosphatase receptor type O expression in the tumor niche correlates with reduced tumor growth, angiogenesis, circulating tumor cells and metastasis of breast cancer. , 2015, Oncology reports.

[197]  P. Steeg,et al.  In Vivo Characterization of Changing Blood-Tumor Barrier Permeability in a Mouse Model of Breast Cancer Metastasis: A Complementary Magnetic Resonance Imaging Approach , 2011, Investigative radiology.

[198]  Samira M. Azarin,et al.  Extracellular matrix mediators of metastatic cell colonization characterized using scaffold mimics of the pre-metastatic niche. , 2016, Acta biomaterialia.

[199]  J. Serody,et al.  C-C chemokine receptor 5 on stromal cells promotes pulmonary metastasis. , 2005, Cancer research.

[200]  Hiroyuki Aburatani,et al.  The S100A8–serum amyloid A3–TLR4 paracrine cascade establishes a pre-metastatic phase , 2008, Nature Cell Biology.

[201]  P. Schlag,et al.  Altered mRNA expression of glycosyltransferases in human colorectal carcinomas and liver metastases , 2000, Gut.

[202]  F. Sánchez-Jiménez,et al.  Monocyte chemoattractant protein-1: a key mediator in inflammatory processes. , 2009, The international journal of biochemistry & cell biology.

[203]  I. Malanchi,et al.  Neutrophils fan cancer's flames , 2015, The EMBO journal.

[204]  Xin Lu,et al.  Chemokine (C-C Motif) Ligand 2 Engages CCR2+ Stromal Cells of Monocytic Origin to Promote Breast Cancer Metastasis to Lung and Bone* , 2009, The Journal of Biological Chemistry.

[205]  C. Logothetis,et al.  Osteoblasts in prostate cancer metastasis to bone , 2005, Nature Reviews Cancer.

[206]  R. Kerbel,et al.  Mouse models of advanced spontaneous metastasis for experimental therapeutics , 2011, Nature Reviews Cancer.

[207]  P. Provero,et al.  Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation. , 2011, The Journal of clinical investigation.

[208]  R. Elble,et al.  Lung Endothelial Dipeptidyl Peptidase IV Promotes Adhesion and Metastasis of Rat Breast Cancer Cells via Tumor Cell Surface-associated Fibronectin* , 1998, The Journal of Biological Chemistry.