Interleukin-6 signalling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in human oral squamous cell carcinoma
Lymph node metastasis is associated with resistance to conventional therapy and poor survival of patients with oral squamous cell carcinoma (OSCC). Although lymphangiogenesis is well known to be associated with the occurrence of lymph node metastasis in various cancers, the precise mechanisms of lym...
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Veröffentlicht in: | The Journal of pathology 2011-09, Vol.225 (1), p.142-150 |
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creator | Shinriki, Satoru Jono, Hirofumi Ueda, Mitsuharu Ota, Kazutoshi Ota, Tomoko Sueyoshi, Takanao Oike, Yuichi Ibusuki, Mutsuko Hiraki, Akimitsu Nakayama, Hideki Shinohara, Masanori Ando, Yukio |
description | Lymph node metastasis is associated with resistance to conventional therapy and poor survival of patients with oral squamous cell carcinoma (OSCC). Although lymphangiogenesis is well known to be associated with the occurrence of lymph node metastasis in various cancers, the precise mechanisms of lymphangiogenesis in OSCC are largely unknown. IL‐6, a potent pro‐inflammatory cytokine, has been shown to play active roles in various cancers, including OSCC. This study aimed to investigate the involvement of IL‐6 signalling in lymphatic metastasis and to evaluate the efficacy of tocilizumab, a humanized anti‐human IL‐6 receptor antibody, as an anti‐lymphangiogenic agent for OSCC. This investigation confirmed that levels of expression of IL‐6 protein and VEGF‐C mRNA in OSCC tissues were significantly correlated with lymph node metastasis in patients with OSCC, as assessed by immunohistochemical analysis and real‐time quantitative RT–PCR. In vitro studies showed that IL‐6 regulated VEGF‐C mRNA expression in a human OSCC cell line, SAS cells, through the phosphoinositide 3‐kinase‐Akt pathway. In addition, treatment with tocilizumab led to markedly reduced VEGF‐C mRNA expression and OSCC‐related lymphangiogenesis in SAS xenografts. Together, these data suggest that tocilizumab acted as expected: it inhibited lymph node metastasis in OSCC by reducing tumour lymphangiogenesis. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
doi_str_mv | 10.1002/path.2935 |
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Although lymphangiogenesis is well known to be associated with the occurrence of lymph node metastasis in various cancers, the precise mechanisms of lymphangiogenesis in OSCC are largely unknown. IL‐6, a potent pro‐inflammatory cytokine, has been shown to play active roles in various cancers, including OSCC. This study aimed to investigate the involvement of IL‐6 signalling in lymphatic metastasis and to evaluate the efficacy of tocilizumab, a humanized anti‐human IL‐6 receptor antibody, as an anti‐lymphangiogenic agent for OSCC. This investigation confirmed that levels of expression of IL‐6 protein and VEGF‐C mRNA in OSCC tissues were significantly correlated with lymph node metastasis in patients with OSCC, as assessed by immunohistochemical analysis and real‐time quantitative RT–PCR. In vitro studies showed that IL‐6 regulated VEGF‐C mRNA expression in a human OSCC cell line, SAS cells, through the phosphoinositide 3‐kinase‐Akt pathway. In addition, treatment with tocilizumab led to markedly reduced VEGF‐C mRNA expression and OSCC‐related lymphangiogenesis in SAS xenografts. Together, these data suggest that tocilizumab acted as expected: it inhibited lymph node metastasis in OSCC by reducing tumour lymphangiogenesis. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</description><identifier>ISSN: 0022-3417</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/path.2935</identifier><identifier>PMID: 21710490</identifier><identifier>CODEN: JPTLAS</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Aged ; Animals ; Antibodies ; Antibodies, Monoclonal - pharmacology ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Biological and medical sciences ; Carcinoma, Squamous Cell - drug therapy ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - physiopathology ; Carcinoma, Squamous Cell - secondary ; Cell survival ; Data processing ; Drug Evaluation, Preclinical - methods ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Hematologic and hematopoietic diseases ; Humans ; Inflammation ; Interleukin 6 ; Interleukin 6 receptors ; Interleukin-6 - physiology ; interleukin-6 receptor ; Investigative techniques, diagnostic techniques (general aspects) ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; lymph node metastasis ; Lymph nodes ; lymphangiogenesis ; Lymphangiogenesis - drug effects ; Lymphangiogenesis - physiology ; Male ; Medical sciences ; Metastases ; Mice ; Mice, SCID ; Middle Aged ; Mouth Neoplasms - drug therapy ; Mouth Neoplasms - genetics ; Mouth Neoplasms - physiopathology ; oral squamous cell carcinoma ; Otorhinolaryngology. Stomatology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Phosphatidylinositol 3-Kinases - physiology ; phosphoinositides ; Phosphorylation - drug effects ; Polymerase chain reaction ; Proto-Oncogene Proteins c-akt - physiology ; RNA, Messenger - genetics ; RNA, Neoplasm - genetics ; Signal transduction ; Signal Transduction - physiology ; tocilizumab ; Tumor Cells, Cultured ; Tumors ; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology ; Vascular Endothelial Growth Factor C - biosynthesis ; Vascular Endothelial Growth Factor C - genetics ; vascular endothelial growth factor-C ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>The Journal of pathology, 2011-09, Vol.225 (1), p.142-150</ispartof><rights>Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4255-2238249389d7ec894b47a1204cb3427c58d1de24495419d6551db118227ff04a3</citedby><cites>FETCH-LOGICAL-c4255-2238249389d7ec894b47a1204cb3427c58d1de24495419d6551db118227ff04a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpath.2935$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpath.2935$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27928,27929,45578,45579</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24404307$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21710490$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shinriki, Satoru</creatorcontrib><creatorcontrib>Jono, Hirofumi</creatorcontrib><creatorcontrib>Ueda, Mitsuharu</creatorcontrib><creatorcontrib>Ota, Kazutoshi</creatorcontrib><creatorcontrib>Ota, Tomoko</creatorcontrib><creatorcontrib>Sueyoshi, Takanao</creatorcontrib><creatorcontrib>Oike, Yuichi</creatorcontrib><creatorcontrib>Ibusuki, Mutsuko</creatorcontrib><creatorcontrib>Hiraki, Akimitsu</creatorcontrib><creatorcontrib>Nakayama, Hideki</creatorcontrib><creatorcontrib>Shinohara, Masanori</creatorcontrib><creatorcontrib>Ando, Yukio</creatorcontrib><title>Interleukin-6 signalling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in human oral squamous cell carcinoma</title><title>The Journal of pathology</title><addtitle>J. Pathol</addtitle><description>Lymph node metastasis is associated with resistance to conventional therapy and poor survival of patients with oral squamous cell carcinoma (OSCC). Although lymphangiogenesis is well known to be associated with the occurrence of lymph node metastasis in various cancers, the precise mechanisms of lymphangiogenesis in OSCC are largely unknown. IL‐6, a potent pro‐inflammatory cytokine, has been shown to play active roles in various cancers, including OSCC. This study aimed to investigate the involvement of IL‐6 signalling in lymphatic metastasis and to evaluate the efficacy of tocilizumab, a humanized anti‐human IL‐6 receptor antibody, as an anti‐lymphangiogenic agent for OSCC. This investigation confirmed that levels of expression of IL‐6 protein and VEGF‐C mRNA in OSCC tissues were significantly correlated with lymph node metastasis in patients with OSCC, as assessed by immunohistochemical analysis and real‐time quantitative RT–PCR. In vitro studies showed that IL‐6 regulated VEGF‐C mRNA expression in a human OSCC cell line, SAS cells, through the phosphoinositide 3‐kinase‐Akt pathway. In addition, treatment with tocilizumab led to markedly reduced VEGF‐C mRNA expression and OSCC‐related lymphangiogenesis in SAS xenografts. Together, these data suggest that tocilizumab acted as expected: it inhibited lymph node metastasis in OSCC by reducing tumour lymphangiogenesis. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</description><subject>Aged</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Squamous Cell - drug therapy</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - physiopathology</subject><subject>Carcinoma, Squamous Cell - secondary</subject><subject>Cell survival</subject><subject>Data processing</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Interleukin 6 receptors</subject><subject>Interleukin-6 - physiology</subject><subject>interleukin-6 receptor</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>lymph node metastasis</subject><subject>Lymph nodes</subject><subject>lymphangiogenesis</subject><subject>Lymphangiogenesis - drug effects</subject><subject>Lymphangiogenesis - physiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metastases</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Middle Aged</subject><subject>Mouth Neoplasms - drug therapy</subject><subject>Mouth Neoplasms - genetics</subject><subject>Mouth Neoplasms - physiopathology</subject><subject>oral squamous cell carcinoma</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Phosphatidylinositol 3-Kinases - physiology</subject><subject>phosphoinositides</subject><subject>Phosphorylation - drug effects</subject><subject>Polymerase chain reaction</subject><subject>Proto-Oncogene Proteins c-akt - physiology</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Neoplasm - genetics</subject><subject>Signal transduction</subject><subject>Signal Transduction - physiology</subject><subject>tocilizumab</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><subject>Vascular Endothelial Growth Factor C - biosynthesis</subject><subject>Vascular Endothelial Growth Factor C - genetics</subject><subject>vascular endothelial growth factor-C</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><issn>0022-3417</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS0EotPCghdA3iDKIq1_43hZjaCtOgIkBlhaHsdJTB1naieUeQjeGYcZygpWtny_c86VDwAvMDrDCJHzrR67MyIpfwQWGMmykJUsH4NFnpGCMiyOwHFK3xBCUnL-FBwRLDBiEi3Az-sw2ujtdOtCUcLk2qC9d6GF0baT16NN8LtOJl8jtKEexs56pz1s43A_drDRZhxisYRpF_IouQR1qKHf9dtOh9YNrQ2_X12A3dTrAIeY1elu0v0wJWis99DoaFwYev0MPGm0T_b54TwBn9-9XS-vitWHy-vlxaowjHBeEEIrwiStZC2sqSTbMKExQcxsKCPC8KrGtSWMSc6wrEvOcb3BuCJENA1imp6A13vfbRzuJptG1bs0r6KDzVupSshSZH-RydP_khgRVHFO5Yy-2aMmDilF26htdL2OuwypuSc196TmnjL78mA7bXpbP5B_isnAqwOQP1_7JupgXPrLMYYYRXPo-Z67d97u_p2oPl6srw7RxV7h0mh_PCh0vFWloIKrr-8v1c36y2otbz4pTH8BKUm7EQ</recordid><startdate>201109</startdate><enddate>201109</enddate><creator>Shinriki, Satoru</creator><creator>Jono, Hirofumi</creator><creator>Ueda, Mitsuharu</creator><creator>Ota, Kazutoshi</creator><creator>Ota, Tomoko</creator><creator>Sueyoshi, Takanao</creator><creator>Oike, Yuichi</creator><creator>Ibusuki, Mutsuko</creator><creator>Hiraki, Akimitsu</creator><creator>Nakayama, Hideki</creator><creator>Shinohara, Masanori</creator><creator>Ando, Yukio</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><scope>BSCLL</scope><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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>201109</creationdate><title>Interleukin-6 signalling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in human oral squamous cell carcinoma</title><author>Shinriki, Satoru ; Jono, Hirofumi ; Ueda, Mitsuharu ; Ota, Kazutoshi ; Ota, Tomoko ; Sueyoshi, Takanao ; Oike, Yuichi ; Ibusuki, Mutsuko ; Hiraki, Akimitsu ; Nakayama, Hideki ; Shinohara, Masanori ; Ando, Yukio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4255-2238249389d7ec894b47a1204cb3427c58d1de24495419d6551db118227ff04a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Aged</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Squamous Cell - drug therapy</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - physiopathology</topic><topic>Carcinoma, Squamous Cell - secondary</topic><topic>Cell survival</topic><topic>Data processing</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Interleukin 6 receptors</topic><topic>Interleukin-6 - physiology</topic><topic>interleukin-6 receptor</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>lymph node metastasis</topic><topic>Lymph nodes</topic><topic>lymphangiogenesis</topic><topic>Lymphangiogenesis - drug effects</topic><topic>Lymphangiogenesis - physiology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metastases</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Middle Aged</topic><topic>Mouth Neoplasms - drug therapy</topic><topic>Mouth Neoplasms - genetics</topic><topic>Mouth Neoplasms - physiopathology</topic><topic>oral squamous cell carcinoma</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Phosphatidylinositol 3-Kinases - physiology</topic><topic>phosphoinositides</topic><topic>Phosphorylation - drug effects</topic><topic>Polymerase chain reaction</topic><topic>Proto-Oncogene Proteins c-akt - physiology</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Neoplasm - genetics</topic><topic>Signal transduction</topic><topic>Signal Transduction - physiology</topic><topic>tocilizumab</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><topic>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</topic><topic>Vascular Endothelial Growth Factor C - biosynthesis</topic><topic>Vascular Endothelial Growth Factor C - genetics</topic><topic>vascular endothelial growth factor-C</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shinriki, Satoru</creatorcontrib><creatorcontrib>Jono, Hirofumi</creatorcontrib><creatorcontrib>Ueda, Mitsuharu</creatorcontrib><creatorcontrib>Ota, Kazutoshi</creatorcontrib><creatorcontrib>Ota, Tomoko</creatorcontrib><creatorcontrib>Sueyoshi, Takanao</creatorcontrib><creatorcontrib>Oike, Yuichi</creatorcontrib><creatorcontrib>Ibusuki, Mutsuko</creatorcontrib><creatorcontrib>Hiraki, Akimitsu</creatorcontrib><creatorcontrib>Nakayama, Hideki</creatorcontrib><creatorcontrib>Shinohara, Masanori</creatorcontrib><creatorcontrib>Ando, Yukio</creatorcontrib><collection>Istex</collection><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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shinriki, Satoru</au><au>Jono, Hirofumi</au><au>Ueda, Mitsuharu</au><au>Ota, Kazutoshi</au><au>Ota, Tomoko</au><au>Sueyoshi, Takanao</au><au>Oike, Yuichi</au><au>Ibusuki, Mutsuko</au><au>Hiraki, Akimitsu</au><au>Nakayama, Hideki</au><au>Shinohara, Masanori</au><au>Ando, Yukio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-6 signalling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in human oral squamous cell carcinoma</atitle><jtitle>The Journal of pathology</jtitle><addtitle>J. Pathol</addtitle><date>2011-09</date><risdate>2011</risdate><volume>225</volume><issue>1</issue><spage>142</spage><epage>150</epage><pages>142-150</pages><issn>0022-3417</issn><eissn>1096-9896</eissn><coden>JPTLAS</coden><abstract>Lymph node metastasis is associated with resistance to conventional therapy and poor survival of patients with oral squamous cell carcinoma (OSCC). Although lymphangiogenesis is well known to be associated with the occurrence of lymph node metastasis in various cancers, the precise mechanisms of lymphangiogenesis in OSCC are largely unknown. IL‐6, a potent pro‐inflammatory cytokine, has been shown to play active roles in various cancers, including OSCC. This study aimed to investigate the involvement of IL‐6 signalling in lymphatic metastasis and to evaluate the efficacy of tocilizumab, a humanized anti‐human IL‐6 receptor antibody, as an anti‐lymphangiogenic agent for OSCC. This investigation confirmed that levels of expression of IL‐6 protein and VEGF‐C mRNA in OSCC tissues were significantly correlated with lymph node metastasis in patients with OSCC, as assessed by immunohistochemical analysis and real‐time quantitative RT–PCR. In vitro studies showed that IL‐6 regulated VEGF‐C mRNA expression in a human OSCC cell line, SAS cells, through the phosphoinositide 3‐kinase‐Akt pathway. In addition, treatment with tocilizumab led to markedly reduced VEGF‐C mRNA expression and OSCC‐related lymphangiogenesis in SAS xenografts. Together, these data suggest that tocilizumab acted as expected: it inhibited lymph node metastasis in OSCC by reducing tumour lymphangiogenesis. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>21710490</pmid><doi>10.1002/path.2935</doi><tpages>9</tpages></addata></record> |
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subjects | Aged Animals Antibodies Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Humanized Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Biological and medical sciences Carcinoma, Squamous Cell - drug therapy Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - physiopathology Carcinoma, Squamous Cell - secondary Cell survival Data processing Drug Evaluation, Preclinical - methods Female Gene expression Gene Expression Regulation, Neoplastic - drug effects Hematologic and hematopoietic diseases Humans Inflammation Interleukin 6 Interleukin 6 receptors Interleukin-6 - physiology interleukin-6 receptor Investigative techniques, diagnostic techniques (general aspects) Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis lymph node metastasis Lymph nodes lymphangiogenesis Lymphangiogenesis - drug effects Lymphangiogenesis - physiology Male Medical sciences Metastases Mice Mice, SCID Middle Aged Mouth Neoplasms - drug therapy Mouth Neoplasms - genetics Mouth Neoplasms - physiopathology oral squamous cell carcinoma Otorhinolaryngology. Stomatology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Phosphatidylinositol 3-Kinases - physiology phosphoinositides Phosphorylation - drug effects Polymerase chain reaction Proto-Oncogene Proteins c-akt - physiology RNA, Messenger - genetics RNA, Neoplasm - genetics Signal transduction Signal Transduction - physiology tocilizumab Tumor Cells, Cultured Tumors Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology Vascular Endothelial Growth Factor C - biosynthesis Vascular Endothelial Growth Factor C - genetics vascular endothelial growth factor-C Xenograft Model Antitumor Assays Xenografts |
title | Interleukin-6 signalling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in human oral squamous cell carcinoma |
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