Migratory neighbors and distant invaders: tumor-associated niche cells.

The cancer environment is comprised of tumor cells as well as a wide network of stromal and vascular cells participating in the cellular and molecular events necessary for invasion and metastasis. Tumor secretory factors can activate the migration of host cells, both near to and far from the primary tumor site, as well as promote the exodus of cells to distant tissues. Thus, the migration of stromal cells and tumor cells among specialized microenvironments takes place throughout tumor and metastatic progression, providing evidence for the systemic nature of a malignancy. Investigations of the tumor-stromal and stromal-stromal cross-talk involved in cellular migration in cancer may lead to the design of novel therapeutic strategies.

[1]  J. Lotem,et al.  Epigenetics and the plasticity of differentiation in normal and cancer stem cells , 2006, Oncogene.

[2]  B. Thiers Tumor-Induced Sentinel Lymph Node Lymphangiogenesis and Increased Lymph Flow Precede Melanoma Metastasis , 2008 .

[3]  S. Rafii,et al.  Contribution of endothelial progenitors and proangiogenic hematopoietic cells to vascularization of tumor and ischemic tissue , 2006, Current opinion in hematology.

[4]  M. Grigorian,et al.  Suppression of Tumor Development and Metastasis Formation in Mice Lacking the S 100 A 4 ( mts 1 ) , 2005 .

[5]  R. Grénman,et al.  Fibroblasts can modulate the phenotype of malignant epithelial cells in vitro. , 1997, Experimental cell research.

[6]  C. Heizmann,et al.  S100 proteins: structure, functions and pathology. , 2002, Frontiers in bioscience : a journal and virtual library.

[7]  A. Gressner,et al.  Tumor‐dependent activation of rodent hepatic stellate cells during experimental melanoma metastasis , 1997, Hepatology.

[8]  Holger Gerhardt,et al.  Pericytes limit tumor cell metastasis. , 2006, The Journal of clinical investigation.

[9]  F. Beuvon,et al.  Anti-colony-stimulating factor-1 antibody staining in primary breast adenocarcinomas correlates with marked inflammatory cell infiltrates and prognosis. , 1994, Journal of the National Cancer Institute.

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

[11]  M. Colombo,et al.  Myeloid cell expansion elicited by the progression of spontaneous mammary carcinomas in c-erbB-2 transgenic BALB/c mice suppresses immune reactivity. , 2003, Blood.

[12]  D. Nolan,et al.  Endothelial Progenitor Cells Control the Angiogenic Switch in Mouse Lung Metastasis , 2008, Science.

[13]  S. Nishikawa,et al.  Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1 , 1996, Nature.

[14]  D. Hanahan,et al.  Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis , 1996, Cell.

[15]  Andrew V. Nguyen,et al.  The Macrophage Growth Factor CSF-1 in Mammary Gland Development and Tumor Progression , 2002, Journal of Mammary Gland Biology and Neoplasia.

[16]  G. Schettini,et al.  CXCR4 Activation Induces Epidermal Growth Factor Receptor Transactivation in an Ovarian Cancer Cell Line , 2004, Annals of the New York Academy of Sciences.

[17]  Alberto Mantovani,et al.  Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. , 2006, European journal of cancer.

[18]  K. Tokoyoda,et al.  Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny. , 2003, Immunity.

[19]  M. Moore,et al.  The role of chemoattraction in cancer metastases. , 2001, BioEssays : news and reviews in molecular, cellular and developmental biology.

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

[21]  P. Sinha,et al.  Reduction of Myeloid-Derived Suppressor Cells and Induction of M1 Macrophages Facilitate the Rejection of Established Metastatic Disease1 , 2005, The Journal of Immunology.

[22]  S. Rafii,et al.  Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[23]  D. Curiel,et al.  Genetically modified CD34+ cells exert a cytotoxic bystander effect on human endothelial and cancer cells. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[24]  K. Titani,et al.  Deregulation of alternative splicing of fibronectin pre-mRNA in malignant human liver tumors. , 1989, The Journal of biological chemistry.

[25]  David Botstein,et al.  Identification of alterations in DNA copy number in host stromal cells during tumor progression , 2006, Proceedings of the National Academy of Sciences.

[26]  Fan Zhang,et al.  Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes , 2006, Nature Medicine.

[27]  T. Suda,et al.  Hematopoietic cells regulate the angiogenic switch during tumorigenesis. , 2005, Blood.

[28]  D. Gabrilovich,et al.  Tumor Associated CD8+ T-Cell Tolerance Induced by Bone Marrow Derived Immature Myeloid Cells , 2005 .

[29]  K. Black,et al.  Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma , 2006, Molecular Cancer.

[30]  W. Gerald,et al.  Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts , 1999, Nature.

[31]  Mark A. Hall,et al.  Hemostasis, Thrombosis, and Vascular Biology Materials and Methods Lacz and Platelet Endothelial Cell Adhesion Molecule 1 (pecam-1) Staining , 2022 .

[32]  T. Ochiya,et al.  Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction. , 2003, Biochemical and biophysical research communications.

[33]  A. Mantovani,et al.  Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. , 1996, Blood.

[34]  P. Hwu,et al.  Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8+ T cell responses by dysregulating antigen-presenting cell maturation. , 1999, Journal of immunology.

[35]  J. Thiery Epithelial–mesenchymal transitions in tumour progression , 2002, Nature Reviews Cancer.

[36]  Mark W. Kieran,et al.  Identification of fibroblast heterogeneity in the tumor microenvironment , 2006, Cancer biology & therapy.

[37]  S. Rafii,et al.  Thrombopoietic Cells and the Bone Marrow Vascular Niche , 2007, Annals of the New York Academy of Sciences.

[38]  T. Tlsty Cell-adhesion-dependent influences on genomic instability and carcinogenesis. , 1998, Current opinion in cell biology.

[39]  M. Sales,et al.  Migration-stimulating factor: a genetically truncated onco-fetal fibronectin isoform expressed by carcinoma and tumor-associated stromal cells. , 2003, Cancer research.

[40]  Mina J. Bissell,et al.  Putting tumours in context , 2001, Nature Reviews Cancer.

[41]  A. George,et al.  Source of oncofetal ED-B-containing fibronectin: implications of production by both tumor and endothelial cells. , 2000, Cancer research.

[42]  T. Hunt,et al.  Bone Marrow Contribution to Tumor-Associated Myofibroblasts and Fibroblasts , 2004, Cancer Research.

[43]  A. Harris,et al.  Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer , 2000, The Journal of pathology.

[44]  B. Annabi,et al.  Angiostatin inhibits monocyte/macrophage migration via disruption of actin cytoskeleton , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[45]  K. Pienta,et al.  Expression of CXCR4 and CXCL12 (SDF‐1) in human prostate cancers (PCa) in vivo , 2003, Journal of cellular biochemistry.

[46]  D. Gabrilovich,et al.  Antigen-Specific Inhibition of CD8+ T Cell Response by Immature Myeloid Cells in Cancer Is Mediated by Reactive Oxygen Species1 , 2004, The Journal of Immunology.

[47]  H. Sakurai,et al.  RANKL-induced CCL22/macrophage-derived chemokine produced from osteoclasts potentially promotes the bone metastasis of lung cancer expressing its receptor CCR4 , 2006, Clinical & Experimental Metastasis.

[48]  M. Karkkainen,et al.  Preexisting Lymphatic Endothelium but not Endothelial Progenitor Cells Are Essential for Tumor Lymphangiogenesis and Lymphatic Metastasis , 2004, Cancer Research.

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

[50]  J. Papkoff,et al.  Regulation of epithelial cell migration and tumor formation by beta-catenin signaling. , 2002, Experimental cell research.

[51]  M. Woodroofe,et al.  Chemokine modulation of matrix metalloproteinase and TIMP production in adult rat brain microglia and a human microglial cell line in vitro , 1999, Glia.

[52]  T. Hsu,et al.  Fibroblast-mediated acceleration of human epithelial tumor growth in vivo. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[53]  S. Karpatkin,et al.  Thrombin Induces the Release of Angiopoietin-1 from Platelets , 2001, Thrombosis and Haemostasis.

[54]  E. Farber The multistep nature of cancer development. , 1984, Cancer research.

[55]  Gideon Rechavi,et al.  A Possible Role for CXCR4 and Its Ligand, the CXC Chemokine Stromal Cell-Derived Factor-1, in the Development of Bone Marrow Metastases in Neuroblastoma1 , 2001, The Journal of Immunology.

[56]  M. Andreeff,et al.  The participation of mesenchymal stem cells in tumor stroma formation and their application as targeted-gene delivery vehicles. , 2007, Handbook of experimental pharmacology.

[57]  R. Hildenbrand,et al.  Urokinase and macrophages in tumour angiogenesis. , 1995, British Journal of Cancer.

[58]  S. Friedman,et al.  Proangiogenic role of tumor‐activated hepatic stellate cells in experimental melanoma metastasis , 2003, Hepatology.

[59]  S. Rafii,et al.  Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization. , 2000, Development.

[60]  C. Lewis,et al.  Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. , 2004, Blood.

[61]  J. Pollard Tumour-educated macrophages promote tumour progression and metastasis , 2004, Nature Reviews Cancer.

[62]  A. Agarwal,et al.  PAR1 Is a Matrix Metalloprotease-1 Receptor that Promotes Invasion and Tumorigenesis of Breast Cancer Cells , 2005, Cell.

[63]  G. Assmann,et al.  Isolation of prostate-derived single cells and cell clusters from human peripheral blood. , 1996, Cancer research.

[64]  M. Grigorian,et al.  Suppression of tumor development and metastasis formation in mice lacking the S100A4(mts1) gene. , 2005, Cancer research.

[65]  W. Seeger,et al.  Circulating Vascular Progenitor Cells Do Not Contribute to Compensatory Lung Growth , 2003, Circulation research.

[66]  Xunbin Wei,et al.  In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment , 2005, Nature.

[67]  A. Sica,et al.  Altered macrophage differentiation and immune dysfunction in tumor development. , 2007, The Journal of clinical investigation.

[68]  A. Harris,et al.  Expression of vascular endothelial growth factor by macrophages is up‐regulated in poorly vascularized areas of breast carcinomas , 2000, The Journal of pathology.

[69]  K. Matsumoto,et al.  Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells: in vitro analysis of tumor-stromal interactions. , 1997, Cancer research.

[70]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[71]  D. Newgreen,et al.  Induction of epithelial to mesenchymal transition in PMC42-LA human breast carcinoma cells by carcinoma-associated fibroblast secreted factors , 2007, Breast Cancer Research.

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

[73]  P. Hein,et al.  Carcinoma-associated fibroblasts stimulate tumor progression of initiated human epithelium , 2000, Breast Cancer Research.

[74]  M. Gleave,et al.  Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts. , 1991, Cancer research.

[75]  S. Hayward,et al.  Malignant transformation in a nontumorigenic human prostatic epithelial cell line. , 2001, Cancer research.

[76]  Luigi Naldini,et al.  Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. , 2007, Blood.

[77]  A. Mantovani,et al.  Analysis of the Gene Expression Profile Activated by the CC Chemokine Ligand 5/RANTES and by Lipopolysaccharide in Human Monocytes1 , 2002, The Journal of Immunology.

[78]  Claus W Heizmann,et al.  S100 proteins: structure, functions and pathology. , 2002, Frontiers in bioscience : a journal and virtual library.

[79]  I. Carr Experimental lymphatic metastasis , 1983, Journal of microscopy.

[80]  B. Williams,et al.  Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. , 2005, Blood.

[81]  L. Liotta,et al.  The significance of hematogenous tumor cell clumps in the metastatic process. , 1976, Cancer research.

[82]  G. Viale,et al.  Differentiation between high- and low-grade astrocytoma using a human recombinant antibody to the extra domain-B of fibronectin. , 2002, The American journal of pathology.

[83]  E. Sahai,et al.  PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE , 2008, Nature Cell Biology.

[84]  A. Krüger,et al.  Tissue inhibitor of metalloproteinases-1 promotes liver metastasis by induction of hepatocyte growth factor signaling. , 2007, Cancer research.

[85]  Ross Tubo,et al.  Mesenchymal stem cells within tumour stroma promote breast cancer metastasis , 2007, Nature.

[86]  P. Friedl,et al.  The biology of cell locomotion within three-dimensional extracellular matrix , 2000, Cellular and Molecular Life Sciences CMLS.

[87]  P. Chambon,et al.  Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[88]  D. Gabrilovich,et al.  Tumor-Associated CD8+ T Cell Tolerance Induced by Bone Marrow-Derived Immature Myeloid Cells1 , 2005, The Journal of Immunology.

[89]  M. Barcellos-Hoff,et al.  Irradiated mammary gland stroma promotes the expression of tumorigenic potential by unirradiated epithelial cells. , 2000, Cancer research.

[90]  Jeffrey W Pollard,et al.  Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases. , 2003, The American journal of pathology.

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

[92]  A. Nagler,et al.  Chemokine receptor CXCR4–dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells , 2005, Nature Immunology.

[93]  I. Amit,et al.  A reciprocal tensin-3–cten switch mediates EGF-driven mammary cell migration , 2007, Nature Cell Biology.

[94]  P. Friedl,et al.  Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro. , 1995, Cancer research.

[95]  J. McGee,et al.  Macrophages in human breast disease: a quantitative immunohistochemical study. , 1988, British Journal of Cancer.

[96]  D. McDonald,et al.  Cellular abnormalities of blood vessels as targets in cancer. , 2005, Current opinion in genetics & development.

[97]  D. Hanahan,et al.  Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. , 2003, The Journal of clinical investigation.

[98]  S. Rafii,et al.  A Few to Flip the Angiogenic Switch , 2008, Science.

[99]  Erik Sahai,et al.  Macrophages promote the invasion of breast carcinoma cells via a colony-stimulating factor-1/epidermal growth factor paracrine loop. , 2005, Cancer research.

[100]  Dennis C. Sgroi,et al.  Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 Secretion , 2005, Cell.

[101]  J. Huot,et al.  Endothelial cell migration during angiogenesis. , 2007, Circulation research.

[102]  A. Chambers,et al.  Osteopontin-induced migration of human mammary epithelial cells involves activation of EGF receptor and multiple signal transduction pathways , 2003, Oncogene.

[103]  H. Maeda,et al.  Nitric oxide and oxygen radicals in infection, inflammation, and cancer. , 1998, Biochemistry. Biokhimiia.

[104]  P. Allavena,et al.  Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. , 2002, Trends in immunology.

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

[106]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[107]  D. Gabrilovich,et al.  Role Of Immature Myeloid Cells in Mechanisms of Immune Evasion In Cancer , 2006, Cancer Immunology, Immunotherapy.

[108]  Andrew V. Nguyen,et al.  Colony-Stimulating Factor 1 Promotes Progression of Mammary Tumors to Malignancy , 2001, The Journal of experimental medicine.

[109]  Y. Ogura,et al.  Vascular endothelial growth factor family and receptor expression in human choroidal neovascular membranes. , 2002, Microvascular research.

[110]  G. Fuh,et al.  Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells , 2007, Nature Biotechnology.

[111]  F. Balkwill,et al.  Chemokine stimulation of monocyte matrix metalloproteinase‐9 requires endogenous TNF‐α  , 2002, European journal of immunology.

[112]  Z. Werb,et al.  Matrix Metalloproteinase Stromelysin-1 Triggers a Cascade of Molecular Alterations That Leads to Stable Epithelial-to-Mesenchymal Conversion and a Premalignant Phenotype in Mammary Epithelial Cells , 1997, The Journal of cell biology.

[113]  M. Noda,et al.  Printed in U.S.A. Copyright © 2001 by The Endocrine Society Osteopontin Facilitates Angiogenesis, Accumulation of , 2000 .

[114]  E. Sahai,et al.  Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells , 2007, Nature Cell Biology.

[115]  M. Stack,et al.  Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion , 2007, Nature Cell Biology.

[116]  Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration , 2003 .

[117]  H. Moses,et al.  Stromal fibroblasts in cancer initiation and progression , 2004, Nature.

[118]  A. Roberts,et al.  Breast cancer cells induce stromal fibroblasts to express MMP-9 via secretion of TNF-α and TGF-β , 2005, Journal of Cell Science.

[119]  Shahin Rafii,et al.  S100 chemokines mediate bookmarking of premetastatic niches , 2006, Nature Cell Biology.

[120]  M. Giacca,et al.  Anti-PlGF Inhibits Growth of VEGF(R)-Inhibitor-Resistant Tumors without Affecting Healthy Vessels , 2007, Cell.

[121]  Luigi Naldini,et al.  Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. , 2005, Cancer cell.

[122]  M. Barcellos-Hoff,et al.  The Potential Influence of Radiation-Induced Microenvironments in Neoplastic Progression , 1998, Journal of Mammary Gland Biology and Neoplasia.

[123]  L. Matrisian,et al.  Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. , 1996, The American journal of pathology.

[124]  R. Strieter,et al.  Infiltration of COX-2-expressing macrophages is a prerequisite for IL-1 beta-induced neovascularization and tumor growth. , 2005, The Journal of clinical investigation.

[125]  M. F. Booth,et al.  What brings pericytes to tumor vessels? , 2003, The Journal of clinical investigation.

[126]  J. Pollard,et al.  Macrophages regulate the angiogenic switch in a mouse model of breast cancer. , 2006, Cancer research.

[127]  A. Harris,et al.  Cytokine networks in solid human tumors: regulation of angiogenesis , 1994, Journal of leukocyte biology.

[128]  Philipp Busch,et al.  Tumor-cell homing to lymph nodes and bone marrow and CXCR4 expression in esophageal cancer. , 2005, Journal of the National Cancer Institute.

[129]  M. Weil,et al.  The CC chemokine RANTES in breast carcinoma progression: regulation of expression and potential mechanisms of promalignant activity. , 2002, Cancer research.

[130]  N. Fusenig,et al.  Friends or foes — bipolar effects of the tumour stroma in cancer , 2004, Nature Reviews Cancer.

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

[132]  D. Scheinberg,et al.  Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization. , 2007, Genes & development.

[133]  Raghu Kalluri,et al.  Fibroblasts in cancer , 2006, Nature Reviews Cancer.

[134]  Yarong Wang,et al.  Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. , 2007, Cancer research.

[135]  P. Dulguerov,et al.  EB-D fibronectin expression in squamous cell carcinoma of the head and neck. , 2005, Oral oncology.

[136]  M. Yoder,et al.  Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. , 2007, Experimental hematology.

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

[138]  D. Carbone,et al.  Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis. , 2008, Cancer cell.

[139]  G. Hannon,et al.  A Proinflammatory Cytokine Inhibits P53 Tumor Suppressor Activity , 1999, The Journal of experimental medicine.

[140]  D. Curiel,et al.  Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses , 2006, Molecular Cancer Therapeutics.

[141]  W. Schürch,et al.  Smooth‐muscle differentiation in stromal cells of malignant and non‐malignant breast tissues , 1988, International journal of cancer.

[142]  Peter Carmeliet,et al.  VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[143]  C. Betsholtz,et al.  Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors. , 2003, The Journal of clinical investigation.

[144]  W. Schaper,et al.  Bone marrow-Derived Cells Do Not Incorporate Into the Adult Growing Vasculature , 2004, Circulation research.

[145]  S. Rafii,et al.  Impaired recruitment of bone-marrow–derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth , 2001, Nature Medicine.

[146]  B. Fingleton,et al.  Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. , 2004, Cancer cell.

[147]  J. Segall,et al.  Intravital imaging of cell movement in tumours , 2003, Nature Reviews Cancer.

[148]  P. Kuo,et al.  The role of Osteopontin in tumor metastasis. , 2004, The Journal of surgical research.

[149]  研宙 大内田,et al.  Radiation to stromal fibroblasts increases invasiveness of pancreatic cancer cells through tumor-stromal interactions , 2005 .