p19/Arf and p53 suppress sentinel lymph node lymphangiogenesis and carcinoma metastasis
The ability of tumor cells to metastasize is increasingly viewed as an interaction between the primary tumor and host tissues. Deletion of the p19/Arf or p53 tumor suppressor genes accelerates malignant progression and metastatic spread of 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoyl-pho...
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| Veröffentlicht in: | Oncogene 2008-05, Vol.27 (22), p.3145-3155 |
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| creator | Ruddell, A Kelly-Spratt, K S Furuya, M Parghi, S S Kemp, C J |
| description | The ability of tumor cells to metastasize is increasingly viewed as an interaction between the primary tumor and host tissues. Deletion of the p19/Arf or p53 tumor suppressor genes accelerates malignant progression and metastatic spread of 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced squamous cell carcinomas, providing a model system to address mechanisms of metastasis. Here, we show that benign pre-metastatic papillomas from wild-type mice trigger lymphangiogenesis within draining lymph nodes, whereas there is no growth of primary tumor lymphatic vessels. Lymph node lymphangiogenesis is greatly accelerated in papilloma-bearing p19/Arf- or p53-deficient mice, which coincides with the greater propensity of these tumors to progress to carcinomas and to metastasize. The extent of accumulation of B cells within the tumor-draining lymph nodes of wild-type mice predicted the level of lymph node lymphangiogenesis and metastatic potential. Arf or p53 deficiency strongly accelerated lymph node immune cell accumulation, in a manner that was associated with the extent of lymph node lymphatic sinus growth. This immune cell accumulation and lymph node lymphangiogenesis phenotype identifies host anti-tumor responses that could drive metastatic spread of cancers via the lymphatics. |
| doi_str_mv | 10.1038/sj.onc.1210973 |
| format | Article |
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Deletion of the p19/Arf or p53 tumor suppressor genes accelerates malignant progression and metastatic spread of 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced squamous cell carcinomas, providing a model system to address mechanisms of metastasis. Here, we show that benign pre-metastatic papillomas from wild-type mice trigger lymphangiogenesis within draining lymph nodes, whereas there is no growth of primary tumor lymphatic vessels. Lymph node lymphangiogenesis is greatly accelerated in papilloma-bearing p19/Arf- or p53-deficient mice, which coincides with the greater propensity of these tumors to progress to carcinomas and to metastasize. The extent of accumulation of B cells within the tumor-draining lymph nodes of wild-type mice predicted the level of lymph node lymphangiogenesis and metastatic potential. Arf or p53 deficiency strongly accelerated lymph node immune cell accumulation, in a manner that was associated with the extent of lymph node lymphatic sinus growth. This immune cell accumulation and lymph node lymphangiogenesis phenotype identifies host anti-tumor responses that could drive metastatic spread of cancers via the lymphatics.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1210973</identifier><identifier>PMID: 18059331</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>9,10-Dimethyl-1,2-benzanthracene ; Acetic acid ; Animals ; Anthracene ; Apoptosis ; B-Lymphocytes - pathology ; Biological and medical sciences ; Cancer ; Carcinoma, Squamous Cell - blood supply ; Carcinoma, Squamous Cell - chemically induced ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - pathology ; Care and treatment ; Cell Biology ; Cell physiology ; Cell Proliferation ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cellular biology ; Chemotaxis, Leukocyte - genetics ; Complications and side effects ; Cyclin-Dependent Kinase Inhibitor p16 - genetics ; Cyclin-Dependent Kinase Inhibitor p16 - physiology ; Diagnosis ; Fundamental and applied biological sciences. Psychology ; Gene mutations ; Genetics ; Health aspects ; Human Genetics ; Internal Medicine ; Lymph nodes ; Lymph Nodes - physiology ; Lymphangiogenesis - genetics ; Lymphatic Metastasis ; Lymphatic system ; Lymphocytes B ; Macrophages - pathology ; Medicine ; Medicine & Public Health ; Metastases ; Metastasis ; Mice ; Mice, Transgenic ; Molecular and cellular biology ; Neovascularization, Pathologic - genetics ; Oncology ; original-article ; p53 Protein ; Papilloma ; Phenotypes ; Risk factors ; Rodents ; Skin Neoplasms - blood supply ; Skin Neoplasms - chemically induced ; Skin Neoplasms - genetics ; Skin Neoplasms - pathology ; Squamous cell carcinoma ; Tetradecanoylphorbol Acetate ; Tumor cells ; Tumor suppressor genes ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - physiology ; Tumors ; Vascular Endothelial Growth Factor A - metabolism</subject><ispartof>Oncogene, 2008-05, Vol.27 (22), p.3145-3155</ispartof><rights>Springer Nature Limited 2008</rights><rights>2008 INIST-CNRS</rights><rights>COPYRIGHT 2008 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 15, 2008</rights><rights>Nature Publishing Group 2008.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c587t-142340a45f19a1a7071002685b3ca565cd21541069625de53d986a6deb0f4bc93</citedby><cites>FETCH-LOGICAL-c587t-142340a45f19a1a7071002685b3ca565cd21541069625de53d986a6deb0f4bc93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.onc.1210973$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.onc.1210973$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20374208$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18059331$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ruddell, A</creatorcontrib><creatorcontrib>Kelly-Spratt, K S</creatorcontrib><creatorcontrib>Furuya, M</creatorcontrib><creatorcontrib>Parghi, S S</creatorcontrib><creatorcontrib>Kemp, C J</creatorcontrib><title>p19/Arf and p53 suppress sentinel lymph node lymphangiogenesis and carcinoma metastasis</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>The ability of tumor cells to metastasize is increasingly viewed as an interaction between the primary tumor and host tissues. Deletion of the p19/Arf or p53 tumor suppressor genes accelerates malignant progression and metastatic spread of 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced squamous cell carcinomas, providing a model system to address mechanisms of metastasis. Here, we show that benign pre-metastatic papillomas from wild-type mice trigger lymphangiogenesis within draining lymph nodes, whereas there is no growth of primary tumor lymphatic vessels. Lymph node lymphangiogenesis is greatly accelerated in papilloma-bearing p19/Arf- or p53-deficient mice, which coincides with the greater propensity of these tumors to progress to carcinomas and to metastasize. The extent of accumulation of B cells within the tumor-draining lymph nodes of wild-type mice predicted the level of lymph node lymphangiogenesis and metastatic potential. Arf or p53 deficiency strongly accelerated lymph node immune cell accumulation, in a manner that was associated with the extent of lymph node lymphatic sinus growth. This immune cell accumulation and lymph node lymphangiogenesis phenotype identifies host anti-tumor responses that could drive metastatic spread of cancers via the lymphatics.</description><subject>9,10-Dimethyl-1,2-benzanthracene</subject><subject>Acetic acid</subject><subject>Animals</subject><subject>Anthracene</subject><subject>Apoptosis</subject><subject>B-Lymphocytes - pathology</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Carcinoma, Squamous Cell - blood supply</subject><subject>Carcinoma, Squamous Cell - chemically induced</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Care and treatment</subject><subject>Cell Biology</subject><subject>Cell physiology</subject><subject>Cell Proliferation</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cellular biology</subject><subject>Chemotaxis, Leukocyte - genetics</subject><subject>Complications and side effects</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - physiology</subject><subject>Diagnosis</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene mutations</subject><subject>Genetics</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Internal Medicine</subject><subject>Lymph nodes</subject><subject>Lymph Nodes - physiology</subject><subject>Lymphangiogenesis - genetics</subject><subject>Lymphatic Metastasis</subject><subject>Lymphatic system</subject><subject>Lymphocytes B</subject><subject>Macrophages - pathology</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Molecular and cellular biology</subject><subject>Neovascularization, Pathologic - genetics</subject><subject>Oncology</subject><subject>original-article</subject><subject>p53 Protein</subject><subject>Papilloma</subject><subject>Phenotypes</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Skin Neoplasms - blood supply</subject><subject>Skin Neoplasms - chemically induced</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - pathology</subject><subject>Squamous cell carcinoma</subject><subject>Tetradecanoylphorbol Acetate</subject><subject>Tumor cells</subject><subject>Tumor suppressor genes</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - physiology</subject><subject>Tumors</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFks1r3DAQxU1paTZprz0W05LedndGn9ZxCf2CQC8tPQqtLG-12LKrWR_y39fumgRKQpFAg_R7bzTwiuINwgaBV1s6bvrkN8gQjObPihUKrdZSGvG8WIGRsDaMs4vikugIANoAe1lcYAXScI6r4ueAZrvLTelSXQ6SlzQOQw5EJYV0iim0ZXvXDb_K1NfhXLp0iP0hpECR_sq8yz6mvnNlF06Oph3pVfGicS2F18t5Vfz49PH7zZf17bfPX292t2svK31ao2BcgBOyQePQadAIwFQl99w7qaSvGUqBoIxisg6S16ZSTtVhD43Ye8Ovig9n3yH3v8dAJ9tF8qFtXQr9SJYhR2lQ_RdEo6UAPju-_wc89mNO0xCWKYG8UlBVE_XuSYpproScJru3Org22Jia_pSdn_vaHWrDdFXp2WrzCDWtOnTR9yk0cbp_TOBzT5RDY4ccO5fvLIKdU2HpaKdU2CUVk-Dt8tlx34X6AV9iMAHXC-DIu7bJLvlI9xwDrgWDufP2zNH0lA4hP0z9ROs_cpbL8g</recordid><startdate>20080515</startdate><enddate>20080515</enddate><creator>Ruddell, A</creator><creator>Kelly-Spratt, K S</creator><creator>Furuya, M</creator><creator>Parghi, S S</creator><creator>Kemp, C J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7T5</scope></search><sort><creationdate>20080515</creationdate><title>p19/Arf and p53 suppress sentinel lymph node lymphangiogenesis and carcinoma metastasis</title><author>Ruddell, A ; Kelly-Spratt, K S ; Furuya, M ; Parghi, S S ; Kemp, C J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c587t-142340a45f19a1a7071002685b3ca565cd21541069625de53d986a6deb0f4bc93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>9,10-Dimethyl-1,2-benzanthracene</topic><topic>Acetic acid</topic><topic>Animals</topic><topic>Anthracene</topic><topic>Apoptosis</topic><topic>B-Lymphocytes - pathology</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Carcinoma, Squamous Cell - blood supply</topic><topic>Carcinoma, Squamous Cell - chemically induced</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Care and treatment</topic><topic>Cell Biology</topic><topic>Cell physiology</topic><topic>Cell Proliferation</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cellular biology</topic><topic>Chemotaxis, Leukocyte - genetics</topic><topic>Complications and side effects</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - physiology</topic><topic>Diagnosis</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene mutations</topic><topic>Genetics</topic><topic>Health aspects</topic><topic>Human Genetics</topic><topic>Internal Medicine</topic><topic>Lymph nodes</topic><topic>Lymph Nodes - physiology</topic><topic>Lymphangiogenesis - genetics</topic><topic>Lymphatic Metastasis</topic><topic>Lymphatic system</topic><topic>Lymphocytes B</topic><topic>Macrophages - pathology</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Molecular and cellular biology</topic><topic>Neovascularization, Pathologic - genetics</topic><topic>Oncology</topic><topic>original-article</topic><topic>p53 Protein</topic><topic>Papilloma</topic><topic>Phenotypes</topic><topic>Risk factors</topic><topic>Rodents</topic><topic>Skin Neoplasms - blood supply</topic><topic>Skin Neoplasms - chemically induced</topic><topic>Skin Neoplasms - genetics</topic><topic>Skin Neoplasms - pathology</topic><topic>Squamous cell carcinoma</topic><topic>Tetradecanoylphorbol Acetate</topic><topic>Tumor cells</topic><topic>Tumor suppressor genes</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - physiology</topic><topic>Tumors</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ruddell, A</creatorcontrib><creatorcontrib>Kelly-Spratt, K S</creatorcontrib><creatorcontrib>Furuya, M</creatorcontrib><creatorcontrib>Parghi, S S</creatorcontrib><creatorcontrib>Kemp, C J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Immunology Abstracts</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ruddell, A</au><au>Kelly-Spratt, K S</au><au>Furuya, M</au><au>Parghi, S S</au><au>Kemp, C J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p19/Arf and p53 suppress sentinel lymph node lymphangiogenesis and carcinoma metastasis</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2008-05-15</date><risdate>2008</risdate><volume>27</volume><issue>22</issue><spage>3145</spage><epage>3155</epage><pages>3145-3155</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>The ability of tumor cells to metastasize is increasingly viewed as an interaction between the primary tumor and host tissues. Deletion of the p19/Arf or p53 tumor suppressor genes accelerates malignant progression and metastatic spread of 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced squamous cell carcinomas, providing a model system to address mechanisms of metastasis. Here, we show that benign pre-metastatic papillomas from wild-type mice trigger lymphangiogenesis within draining lymph nodes, whereas there is no growth of primary tumor lymphatic vessels. Lymph node lymphangiogenesis is greatly accelerated in papilloma-bearing p19/Arf- or p53-deficient mice, which coincides with the greater propensity of these tumors to progress to carcinomas and to metastasize. The extent of accumulation of B cells within the tumor-draining lymph nodes of wild-type mice predicted the level of lymph node lymphangiogenesis and metastatic potential. Arf or p53 deficiency strongly accelerated lymph node immune cell accumulation, in a manner that was associated with the extent of lymph node lymphatic sinus growth. This immune cell accumulation and lymph node lymphangiogenesis phenotype identifies host anti-tumor responses that could drive metastatic spread of cancers via the lymphatics.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>18059331</pmid><doi>10.1038/sj.onc.1210973</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 9,10-Dimethyl-1,2-benzanthracene Acetic acid Animals Anthracene Apoptosis B-Lymphocytes - pathology Biological and medical sciences Cancer Carcinoma, Squamous Cell - blood supply Carcinoma, Squamous Cell - chemically induced Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Care and treatment Cell Biology Cell physiology Cell Proliferation Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cellular biology Chemotaxis, Leukocyte - genetics Complications and side effects Cyclin-Dependent Kinase Inhibitor p16 - genetics Cyclin-Dependent Kinase Inhibitor p16 - physiology Diagnosis Fundamental and applied biological sciences. Psychology Gene mutations Genetics Health aspects Human Genetics Internal Medicine Lymph nodes Lymph Nodes - physiology Lymphangiogenesis - genetics Lymphatic Metastasis Lymphatic system Lymphocytes B Macrophages - pathology Medicine Medicine & Public Health Metastases Metastasis Mice Mice, Transgenic Molecular and cellular biology Neovascularization, Pathologic - genetics Oncology original-article p53 Protein Papilloma Phenotypes Risk factors Rodents Skin Neoplasms - blood supply Skin Neoplasms - chemically induced Skin Neoplasms - genetics Skin Neoplasms - pathology Squamous cell carcinoma Tetradecanoylphorbol Acetate Tumor cells Tumor suppressor genes Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - physiology Tumors Vascular Endothelial Growth Factor A - metabolism |
| title | p19/Arf and p53 suppress sentinel lymph node lymphangiogenesis and carcinoma metastasis |
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