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  • 1
    Abstract: The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (〈5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (〈12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.
    Type of Publication: Journal article published
    PubMed ID: 26760213
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  • 2
    Keywords: MODEL ; chemotherapy ; CHILDREN ; SUBTYPES ; GLIOBLASTOMA ; INTRATUMORAL HETEROGENEITY ; RISK MEDULLOBLASTOMA
    Abstract: Medulloblastoma comprises four distinct molecular variants with distinct genetics, transcriptomes, and outcomes. Subgroup affiliation has been previously shown to remain stable at the time of recurrence, which likely reflects their distinct cells of origin. However, a therapeutically relevant question that remains unanswered is subgroup stability in the metastatic compartment. We assembled a cohort of 12-paired primary-metastatic tumors collected in the MAGIC consortium, and established their molecular subgroup affiliation by performing integrative gene expression and DNA methylation analysis. Frozen tissues were collected and profiled using Affymetrix gene expression arrays and Illumina methylation arrays. Class prediction and hierarchical clustering were performed using existing published datasets. Our molecular analysis, using consensus integrative genomic data, establishes the unequivocal maintenance of molecular subgroup affiliation in metastatic medulloblastoma. We further validated these findings by interrogating a non-overlapping cohort of 19 pairs of primary-metastatic tumors from the Burdenko Neurosurgical Institute using an orthogonal technique of immunohistochemical staining. This investigation represents the largest reported primary-metastatic paired cohort profiled to date and provides a unique opportunity to evaluate subgroup-specific molecular aberrations within the metastatic compartment. Our findings further support the hypothesis that medulloblastoma subgroups arise from distinct cells of origin, which are carried forward from ontogeny to oncology.
    Type of Publication: Journal article published
    PubMed ID: 25689980
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  • 3
  • 4
    Publication Date: 2016-01-14
    Description: The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (〈5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (〈12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morrissy, A Sorana -- Garzia, Livia -- Shih, David J H -- Zuyderduyn, Scott -- Huang, Xi -- Skowron, Patryk -- Remke, Marc -- Cavalli, Florence M G -- Ramaswamy, Vijay -- Lindsay, Patricia E -- Jelveh, Salomeh -- Donovan, Laura K -- Wang, Xin -- Luu, Betty -- Zayne, Kory -- Li, Yisu -- Mayoh, Chelsea -- Thiessen, Nina -- Mercier, Eloi -- Mungall, Karen L -- Ma, Yusanne -- Tse, Kane -- Zeng, Thomas -- Shumansky, Karey -- Roth, Andrew J L -- Shah, Sohrab -- Farooq, Hamza -- Kijima, Noriyuki -- Holgado, Borja L -- Lee, John J Y -- Matan-Lithwick, Stuart -- Liu, Jessica -- Mack, Stephen C -- Manno, Alex -- Michealraj, K A -- Nor, Carolina -- Peacock, John -- Qin, Lei -- Reimand, Juri -- Rolider, Adi -- Thompson, Yuan Y -- Wu, Xiaochong -- Pugh, Trevor -- Ally, Adrian -- Bilenky, Mikhail -- Butterfield, Yaron S N -- Carlsen, Rebecca -- Cheng, Young -- Chuah, Eric -- Corbett, Richard D -- Dhalla, Noreen -- He, An -- Lee, Darlene -- Li, Haiyan I -- Long, William -- Mayo, Michael -- Plettner, Patrick -- Qian, Jenny Q -- Schein, Jacqueline E -- Tam, Angela -- Wong, Tina -- Birol, Inanc -- Zhao, Yongjun -- Faria, Claudia C -- Pimentel, Jose -- Nunes, Sofia -- Shalaby, Tarek -- Grotzer, Michael -- Pollack, Ian F -- Hamilton, Ronald L -- Li, Xiao-Nan -- Bendel, Anne E -- Fults, Daniel W -- Walter, Andrew W -- Kumabe, Toshihiro -- Tominaga, Teiji -- Collins, V Peter -- Cho, Yoon-Jae -- Hoffman, Caitlin -- Lyden, David -- Wisoff, Jeffrey H -- Garvin, James H Jr -- Stearns, Duncan S -- Massimi, Luca -- Schuller, Ulrich -- Sterba, Jaroslav -- Zitterbart, Karel -- Puget, Stephanie -- Ayrault, Olivier -- Dunn, Sandra E -- Tirapelli, Daniela P C -- Carlotti, Carlos G -- Wheeler, Helen -- Hallahan, Andrew R -- Ingram, Wendy -- MacDonald, Tobey J -- Olson, Jeffrey J -- Van Meir, Erwin G -- Lee, Ji-Yeoun -- Wang, Kyu-Chang -- Kim, Seung-Ki -- Cho, Byung-Kyu -- Pietsch, Torsten -- Fleischhack, Gudrun -- Tippelt, Stephan -- Ra, Young Shin -- Bailey, Simon -- Lindsey, Janet C -- Clifford, Steven C -- Eberhart, Charles G -- Cooper, Michael K -- Packer, Roger J -- Massimino, Maura -- Garre, Maria Luisa -- Bartels, Ute -- Tabori, Uri -- Hawkins, Cynthia E -- Dirks, Peter -- Bouffet, Eric -- Rutka, James T -- Wechsler-Reya, Robert J -- Weiss, William A -- Collier, Lara S -- Dupuy, Adam J -- Korshunov, Andrey -- Jones, David T W -- Kool, Marcel -- Northcott, Paul A -- Pfister, Stefan M -- Largaespada, David A -- Mungall, Andrew J -- Moore, Richard A -- Jabado, Nada -- Bader, Gary D -- Jones, Steven J M -- Malkin, David -- Marra, Marco A -- Taylor, Michael D -- R01 CA163722/CA/NCI NIH HHS/ -- R01 NS096236/NS/NINDS NIH HHS/ -- R01CA148699/CA/NCI NIH HHS/ -- R01CA159859/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2016 Jan 21;529(7586):351-7. doi: 10.1038/nature16478. Epub 2016 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada. ; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. ; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 0A4, Canada. ; The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. ; Department of Pediatric Oncology, Hematology, and Clinical Immunology, University Hospital Dusseldorf, M5S 3E1, Germany. ; Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario M5S 3E1, Canada. ; Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9, Canada. ; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 2M9, Canada. ; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada. ; Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada. ; Center for Stem Cell &Regenerative Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. ; Clinical Genomics Research Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario 44195, Canada. ; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. ; School of Computing Science, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada. ; Division of Neurosurgery, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon 1649-035, Portugal. ; Divison of Pathology, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon 1649-035, Portugal. ; Unidade de Neuro-Oncologia Pediatrica, Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Lisbon 1099-023, Portugal. ; Departments of Oncology and Neuro-Oncology, University Children's Hospital of Zurich, Zurich 8032, Switzerland. ; Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224, USA. ; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. ; Brain Tumor Program, Children's Cancer Center and Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. ; Pediatric Hematology-Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota 55404, USA. ; Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah 84132, USA. ; A I duPont Hospital for Children, Wilmington, Delaware 19803, USA. ; Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan. ; Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan. ; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK. ; Departments of Neurosurgery, Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA. ; Departments of Pediatrics, Cell &Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, USA. ; Department of Neurosurgery, NYU Langone Medical Center, New York, New York 10016, USA. ; Department of Pediatrics, Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University, New York, New York 10032, USA. ; Department of Pediatrics-Hematology and Oncology, Rainbow Babies &Children's Hospital and Department of Pediatrics-Hematology and Oncology, Case Western Reserve, Cleveland, Ohio 44106, USA. ; Pediatric Neurosurgery, Catholic University Medical School, Rome 00198, Italy. ; Center for Neuropathology, Ludwig-Maximilians-Universitat, Munich 81377, Germany. ; Department of Pediatric Oncology, School of Medicine, Masaryk University, Brno 625 00, Czech Republic. ; AP-HP, Department of Neurosurgery, Necker-Enfants Malades Hospital, Universite Rene Descartes, Paris 75743, France. ; Signaling in Development and Brain Tumors, CNRS UMR 3347 / INSERM U1021, Institut Curie, Paris Cedex 5 91405, France. ; Division of Hematology/Oncology, British Columbia Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada. ; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirao Preto, Universidade de Sao Paulo, Brazil, Rebeirao Preto, Sao Paulo 14049-900, Brazil. ; Kolling Institute of Medical Research, The University of Sydney, Sydney, New South Wales 2065, Australia. ; Queensland Children's Medical Research Institute, Children's Health Queensland, Brisbane, Queensland 4029, Australia. ; Division of Oncology, Children's Health Queensland, Brisbane, Queensland 4029, Australia. ; UQ Child Health Research Centre, The University of Queensland, Brisbane 4029, Australia. ; Pediatric Neuro-Oncology Program, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia 30307, USA. ; Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA. ; Department of Hematology &Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA. ; Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 30322, South Korea. ; Institute for Neuropathology, University of Bonn D-53105, Germany. ; Children's University Hospital of Essen D-45147, Germany. ; Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul 05505, South Korea. ; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE1 4LP, UK. ; Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Neurology, Vanderbilt Medical Center, Nashville, Tennessee 37232-8550, USA. ; Department of Neurology, Children's National Medical Center, Washington DC 20010-2970, USA. ; Fondazione IRCCS Istituto Nazionale Tumori, Milan 20133, Italy. ; U.O. Neurochirurgia, Istituto Giannina Gaslini, Genova 16147, Italy. ; Department of Haematology &Oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. ; Division of Pathology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. ; Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA. ; Departments of Pediatrics, Neurology and Neurosurgery, University of California San Francisco, San Francisco, California 94158, USA. ; School of Pharmacology, University of Wisconsin, Madison, Wisconsin 53715, USA. ; Molecular &Cellular Biology Program, University of Iowa, Iowa City, Iowa 52242, USA. ; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; Department of Pediatric Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany. ; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA. ; Division of Hematology/Oncology, McGill University, Montreal, Quebec H2W 1S6., Canada. ; McLaughlin Centre and Department of Molecular Genetics, Banting and Best Department of Medical Research and Samuel Lunenfeld Research Institute at Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1L7, Canada. ; Department of Molecular Biology &Biochemistry, Simon Fraser University, Burnaby, British Columbia M5G 1L7, Canada. ; Department of Pediatrics, University of Toronto, Toronto, Ontario M5G 1X8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26760213" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2015-11-03
    Description: Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins alpha6beta4 and alpha6beta1 were associated with lung metastasis, while exosomal integrin alphavbeta5 was linked to liver metastasis. Targeting the integrins alpha6beta4 and alphavbeta5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoshino, Ayuko -- Costa-Silva, Bruno -- Shen, Tang-Long -- Rodrigues, Goncalo -- Hashimoto, Ayako -- Tesic Mark, Milica -- Molina, Henrik -- Kohsaka, Shinji -- Di Giannatale, Angela -- Ceder, Sophia -- Singh, Swarnima -- Williams, Caitlin -- Soplop, Nadine -- Uryu, Kunihiro -- Pharmer, Lindsay -- King, Tari -- Bojmar, Linda -- Davies, Alexander E -- Ararso, Yonathan -- Zhang, Tuo -- Zhang, Haiying -- Hernandez, Jonathan -- Weiss, Joshua M -- Dumont-Cole, Vanessa D -- Kramer, Kimberly -- Wexler, Leonard H -- Narendran, Aru -- Schwartz, Gary K -- Healey, John H -- Sandstrom, Per -- Labori, Knut Jorgen -- Kure, Elin H -- Grandgenett, Paul M -- Hollingsworth, Michael A -- de Sousa, Maria -- Kaur, Sukhwinder -- Jain, Maneesh -- Mallya, Kavita -- Batra, Surinder K -- Jarnagin, William R -- Brady, Mary S -- Fodstad, Oystein -- Muller, Volkmar -- Pantel, Klaus -- Minn, Andy J -- Bissell, Mina J -- Garcia, Benjamin A -- Kang, Yibin -- Rajasekhar, Vinagolu K -- Ghajar, Cyrus M -- Matei, Irina -- Peinado, Hector -- Bromberg, Jacqueline -- Lyden, David -- R01 CA169416/CA/NCI NIH HHS/ -- R01-CA169416/CA/NCI NIH HHS/ -- U01 CA169538/CA/NCI NIH HHS/ -- U01-CA169538/CA/NCI NIH HHS/ -- England -- Nature. 2015 Nov 19;527(7578):329-35. doi: 10.1038/nature15756. Epub 2015 Oct 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA. ; Department of Plant Pathology and Microbiology and Center for Biotechnology, National Taiwan University, Taipei 10617, Taiwan. ; Graduate Program in Areas of Basic and Applied Biology, Abel Salazar Biomedical Sciences Institute, University of Porto, 4099-003 Porto, Portugal. ; Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan. ; Proteomics Resource Center, The Rockefeller University, New York, New York 10065, USA. ; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Department of Oncology and Pathology, Karolinska Institutet, 17176 Stockholm, Sweden. ; Electron Microscopy Resource Center (EMRC), Rockefeller University, New York, New York 10065, USA. ; Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, USA. ; Department of Surgery, County Council of Ostergotland, and Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, 58185 Linkoping, Sweden. ; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. ; Genomics Resources Core Facility, Weill Cornell Medicine, New York, New York 10021, USA. ; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Division of Pediatric Oncology, Alberta Children's Hospital, Calgary, Alberta T3B 6A8, Canada. ; Division of Hematology/Oncology, Columbia University School of Medicine, New York, New York 10032, USA. ; Orthopaedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Nydalen, Oslo 0424, Norway. ; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Nydalen, Oslo 0424, Norway. ; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA. ; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA. ; Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Nydalen, Oslo 0424, Norway. ; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Blindern, Oslo 0318, Norway. ; Department of Gynecology, University Medical Center, Martinistrasse 52, 20246 Hamburg, Germany. ; Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. ; Department of Radiation Oncology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA. ; Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA. ; Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; Microenvironment and Metastasis Laboratory, Department of Molecular Oncology, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain. ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Department of Medicine, Weill Cornell Medicine, New York, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26524530" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers/metabolism ; Brain/cytology/*metabolism ; Cell Line, Tumor ; Endothelial Cells/cytology/metabolism ; Epithelial Cells/cytology/metabolism ; Exosomes/*metabolism ; Female ; Fibroblasts/cytology/metabolism ; Genes, src ; Humans ; Integrin alpha6beta1/metabolism ; Integrin alpha6beta4/antagonists & inhibitors/metabolism ; Integrin beta Chains/metabolism ; Integrin beta4/metabolism ; Integrins/antagonists & inhibitors/*metabolism ; Kupffer Cells/cytology/metabolism ; Liver/cytology/*metabolism ; Lung/cytology/*metabolism ; Mice ; Mice, Inbred C57BL ; Neoplasm Metastasis/*pathology/*prevention & control ; Organ Specificity ; Phosphorylation ; Receptors, Vitronectin/antagonists & inhibitors/metabolism ; S100 Proteins/genetics ; *Tropism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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