CXCL12 and CXCR4, but not CXCR7, are primarily expressed by the stroma in head and neck squamous cell carcinoma
The CXCL12/CXCR4 axis is involved in numerous models of metastatic dissemination, including head and neck squamous cell carcinoma (HNSCC). We assessed the relative expressions of CXCL12, CXCR4 and CXCR7 in the stroma and the tumour of HNSCC, and evaluated the methylation status of the CXCL12 promote...
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| Veröffentlicht in: | Pathology 2015-01, Vol.47 (1), p.45-50 |
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| creator | Clatot, Florian Cornic, Marie Berghian, Anca Marchand, Vinciane Choussy, Olivier El Ouakif, Faissal François, Arnaud Ruminy, Philippe Laberge-Le-Couteulx, Sophie Picquenot, Jean-Michel Jardin, Fabrice |
| description | The CXCL12/CXCR4 axis is involved in numerous models of metastatic dissemination, including head and neck squamous cell carcinoma (HNSCC). We assessed the relative expressions of CXCL12, CXCR4 and CXCR7 in the stroma and the tumour of HNSCC, and evaluated the methylation status of the CXCL12 promoter. Snap-frozen, HPV negative HNSCC samples were micro-dissected to isolate the tumoural and stromal compartments. The expression levels of CXCL12, CXCR4 and CXCR7 were assessed by qRT-PCR, and the methylation level of the CXCL12 promoter was evaluated by pyrosequencing. In total, 23 matched tumour/stroma samples were analysed. Higher expressions of CXCR4 and CXCL12 were observed in the stroma (p = 0.012 and p < 0.0001, respectively). No significant difference in expression was observed for CXCR7. A high meth-ylation level (>40%) of the CXCL12 promoter was observed in onlya few tumoural samples (5/23) and was associated with a lower expression of the gene (p = 0.03). Stromal cells, rather than the tumour itself, are mainly responsible for the expression of both CXCL12 and CXCR4 expression in HNSCC. CXCR7 expression did not differ between the two compartments and was not related to CXCL12 or CXCR4 expression. Finally, the methylation of the CXCL12 promoter could only explain the low intra-tumoural expression of this gene in 20% of cases. |
| doi_str_mv | 10.1097/PAT.0000000000000191 |
| format | Article |
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We assessed the relative expressions of CXCL12, CXCR4 and CXCR7 in the stroma and the tumour of HNSCC, and evaluated the methylation status of the CXCL12 promoter. Snap-frozen, HPV negative HNSCC samples were micro-dissected to isolate the tumoural and stromal compartments. The expression levels of CXCL12, CXCR4 and CXCR7 were assessed by qRT-PCR, and the methylation level of the CXCL12 promoter was evaluated by pyrosequencing. In total, 23 matched tumour/stroma samples were analysed. Higher expressions of CXCR4 and CXCL12 were observed in the stroma (p = 0.012 and p < 0.0001, respectively). No significant difference in expression was observed for CXCR7. A high meth-ylation level (>40%) of the CXCL12 promoter was observed in onlya few tumoural samples (5/23) and was associated with a lower expression of the gene (p = 0.03). Stromal cells, rather than the tumour itself, are mainly responsible for the expression of both CXCL12 and CXCR4 expression in HNSCC. CXCR7 expression did not differ between the two compartments and was not related to CXCL12 or CXCR4 expression. Finally, the methylation of the CXCL12 promoter could only explain the low intra-tumoural expression of this gene in 20% of cases.</description><identifier>ISSN: 0031-3025</identifier><identifier>EISSN: 1465-3931</identifier><identifier>DOI: 10.1097/PAT.0000000000000191</identifier><identifier>PMID: 25474514</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Adult ; Aged ; Biochemistry, Molecular Biology ; Biomarkers, Tumor - analysis ; Cancer ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Chemokine CXCL12 - analysis ; Chemokine CXCL12 - biosynthesis ; Chemokine CXCL12 - genetics ; CXCL12 ; CXCR4 ; CXCR7 ; DNA Methylation ; Female ; head and neck cancer ; Head and Neck Neoplasms - genetics ; Head and Neck Neoplasms - metabolism ; Head and Neck Neoplasms - pathology ; Humans ; Immunohistochemistry ; laser microdissection ; Life Sciences ; Male ; Microdissection ; Middle Aged ; Neoplasm Invasiveness ; oral cancer ; Promoter Regions, Genetic ; Receptors, CXCR - analysis ; Receptors, CXCR - biosynthesis ; Receptors, CXCR4 - analysis ; Receptors, CXCR4 - biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; SDF-1 ; Squamous Cell Carcinoma of Head and Neck ; stroma ; Tumor Microenvironment - physiology</subject><ispartof>Pathology, 2015-01, Vol.47 (1), p.45-50</ispartof><rights>2015 Royal College of Pathologists of Australasia</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-e841e26b89fd345023843112b27bd9c29a3e6c50ab8c23b595cb9fafb9180cee3</citedby><cites>FETCH-LOGICAL-c396t-e841e26b89fd345023843112b27bd9c29a3e6c50ab8c23b595cb9fafb9180cee3</cites><orcidid>0000-0002-7074-9282</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25474514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://normandie-univ.hal.science/hal-02317968$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Clatot, Florian</creatorcontrib><creatorcontrib>Cornic, Marie</creatorcontrib><creatorcontrib>Berghian, Anca</creatorcontrib><creatorcontrib>Marchand, Vinciane</creatorcontrib><creatorcontrib>Choussy, Olivier</creatorcontrib><creatorcontrib>El Ouakif, Faissal</creatorcontrib><creatorcontrib>François, Arnaud</creatorcontrib><creatorcontrib>Ruminy, Philippe</creatorcontrib><creatorcontrib>Laberge-Le-Couteulx, Sophie</creatorcontrib><creatorcontrib>Picquenot, Jean-Michel</creatorcontrib><creatorcontrib>Jardin, Fabrice</creatorcontrib><title>CXCL12 and CXCR4, but not CXCR7, are primarily expressed by the stroma in head and neck squamous cell carcinoma</title><title>Pathology</title><addtitle>Pathology</addtitle><description>The CXCL12/CXCR4 axis is involved in numerous models of metastatic dissemination, including head and neck squamous cell carcinoma (HNSCC). We assessed the relative expressions of CXCL12, CXCR4 and CXCR7 in the stroma and the tumour of HNSCC, and evaluated the methylation status of the CXCL12 promoter. Snap-frozen, HPV negative HNSCC samples were micro-dissected to isolate the tumoural and stromal compartments. The expression levels of CXCL12, CXCR4 and CXCR7 were assessed by qRT-PCR, and the methylation level of the CXCL12 promoter was evaluated by pyrosequencing. In total, 23 matched tumour/stroma samples were analysed. Higher expressions of CXCR4 and CXCL12 were observed in the stroma (p = 0.012 and p < 0.0001, respectively). No significant difference in expression was observed for CXCR7. A high meth-ylation level (>40%) of the CXCL12 promoter was observed in onlya few tumoural samples (5/23) and was associated with a lower expression of the gene (p = 0.03). Stromal cells, rather than the tumour itself, are mainly responsible for the expression of both CXCL12 and CXCR4 expression in HNSCC. CXCR7 expression did not differ between the two compartments and was not related to CXCL12 or CXCR4 expression. Finally, the methylation of the CXCL12 promoter could only explain the low intra-tumoural expression of this gene in 20% of cases.</description><subject>Adult</subject><subject>Aged</subject><subject>Biochemistry, Molecular Biology</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Cancer</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Chemokine CXCL12 - analysis</subject><subject>Chemokine CXCL12 - biosynthesis</subject><subject>Chemokine CXCL12 - genetics</subject><subject>CXCL12</subject><subject>CXCR4</subject><subject>CXCR7</subject><subject>DNA Methylation</subject><subject>Female</subject><subject>head and neck cancer</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Head and Neck Neoplasms - metabolism</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>laser microdissection</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Microdissection</subject><subject>Middle Aged</subject><subject>Neoplasm Invasiveness</subject><subject>oral cancer</subject><subject>Promoter Regions, Genetic</subject><subject>Receptors, CXCR - analysis</subject><subject>Receptors, CXCR - biosynthesis</subject><subject>Receptors, CXCR4 - analysis</subject><subject>Receptors, CXCR4 - biosynthesis</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>SDF-1</subject><subject>Squamous Cell Carcinoma of Head and Neck</subject><subject>stroma</subject><subject>Tumor Microenvironment - physiology</subject><issn>0031-3025</issn><issn>1465-3931</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV1LHDEUhoO01K32H0jJpQVH8zmT3AjLYmthoSIWeheSzBk2dj7WZEa6_96so1J60dwk5_Cc95yTF6ETSs4p0dXFzfLunPx9qKYHaEFFKQuuOX2HFoRwWnDC5CH6mNJ9ZoRS6gM6ZFJUQlKxQMPq12pNGbZ9jfPzVpxhN424H8bnsDrDNgLextDZGNodhj_bCClBjd0OjxvAaYxDZ3Ho8QZs_azTg_-N08Nku2FK2EPbYm-jD30Gj9H7xrYJPr3cR-jn16u71XWx_vHt-2q5LjzX5ViAEhRY6ZRuai4kYVwJTilzrHK19kxbDqWXxDrlGXdSS-90YxunqSIegB-hL7PuxrZmHn9nBhvM9XJt9rksSStdqkea2dOZ3cbhYYI0mi6k_di2h7yBoSWvpNSqEhkVM-rjkFKE5k2bErO3xWRbzL-25LLPLx0m10H9VvTqQwYuZwDynzwGiCb5AL2HOkTwo6mH8P8OT6ulmKs</recordid><startdate>201501</startdate><enddate>201501</enddate><creator>Clatot, Florian</creator><creator>Cornic, Marie</creator><creator>Berghian, Anca</creator><creator>Marchand, Vinciane</creator><creator>Choussy, Olivier</creator><creator>El Ouakif, Faissal</creator><creator>François, Arnaud</creator><creator>Ruminy, Philippe</creator><creator>Laberge-Le-Couteulx, Sophie</creator><creator>Picquenot, Jean-Michel</creator><creator>Jardin, Fabrice</creator><general>Elsevier B.V</general><general>Elsevier</general><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>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-7074-9282</orcidid></search><sort><creationdate>201501</creationdate><title>CXCL12 and CXCR4, but not CXCR7, are primarily expressed by the stroma in head and neck squamous cell carcinoma</title><author>Clatot, Florian ; Cornic, Marie ; Berghian, Anca ; Marchand, Vinciane ; Choussy, Olivier ; El Ouakif, Faissal ; François, Arnaud ; Ruminy, Philippe ; Laberge-Le-Couteulx, Sophie ; Picquenot, Jean-Michel ; Jardin, Fabrice</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-e841e26b89fd345023843112b27bd9c29a3e6c50ab8c23b595cb9fafb9180cee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biochemistry, Molecular Biology</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Cancer</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Chemokine CXCL12 - analysis</topic><topic>Chemokine CXCL12 - biosynthesis</topic><topic>Chemokine CXCL12 - genetics</topic><topic>CXCL12</topic><topic>CXCR4</topic><topic>CXCR7</topic><topic>DNA Methylation</topic><topic>Female</topic><topic>head and neck cancer</topic><topic>Head and Neck Neoplasms - genetics</topic><topic>Head and Neck Neoplasms - metabolism</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>laser microdissection</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Microdissection</topic><topic>Middle Aged</topic><topic>Neoplasm Invasiveness</topic><topic>oral cancer</topic><topic>Promoter Regions, Genetic</topic><topic>Receptors, CXCR - analysis</topic><topic>Receptors, CXCR - biosynthesis</topic><topic>Receptors, CXCR4 - analysis</topic><topic>Receptors, CXCR4 - biosynthesis</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>SDF-1</topic><topic>Squamous Cell Carcinoma of Head and Neck</topic><topic>stroma</topic><topic>Tumor Microenvironment - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Clatot, Florian</creatorcontrib><creatorcontrib>Cornic, Marie</creatorcontrib><creatorcontrib>Berghian, Anca</creatorcontrib><creatorcontrib>Marchand, Vinciane</creatorcontrib><creatorcontrib>Choussy, Olivier</creatorcontrib><creatorcontrib>El Ouakif, Faissal</creatorcontrib><creatorcontrib>François, Arnaud</creatorcontrib><creatorcontrib>Ruminy, Philippe</creatorcontrib><creatorcontrib>Laberge-Le-Couteulx, Sophie</creatorcontrib><creatorcontrib>Picquenot, Jean-Michel</creatorcontrib><creatorcontrib>Jardin, Fabrice</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Clatot, Florian</au><au>Cornic, Marie</au><au>Berghian, Anca</au><au>Marchand, Vinciane</au><au>Choussy, Olivier</au><au>El Ouakif, Faissal</au><au>François, Arnaud</au><au>Ruminy, Philippe</au><au>Laberge-Le-Couteulx, Sophie</au><au>Picquenot, Jean-Michel</au><au>Jardin, Fabrice</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CXCL12 and CXCR4, but not CXCR7, are primarily expressed by the stroma in head and neck squamous cell carcinoma</atitle><jtitle>Pathology</jtitle><addtitle>Pathology</addtitle><date>2015-01</date><risdate>2015</risdate><volume>47</volume><issue>1</issue><spage>45</spage><epage>50</epage><pages>45-50</pages><issn>0031-3025</issn><eissn>1465-3931</eissn><abstract>The CXCL12/CXCR4 axis is involved in numerous models of metastatic dissemination, including head and neck squamous cell carcinoma (HNSCC). We assessed the relative expressions of CXCL12, CXCR4 and CXCR7 in the stroma and the tumour of HNSCC, and evaluated the methylation status of the CXCL12 promoter. Snap-frozen, HPV negative HNSCC samples were micro-dissected to isolate the tumoural and stromal compartments. The expression levels of CXCL12, CXCR4 and CXCR7 were assessed by qRT-PCR, and the methylation level of the CXCL12 promoter was evaluated by pyrosequencing. In total, 23 matched tumour/stroma samples were analysed. Higher expressions of CXCR4 and CXCL12 were observed in the stroma (p = 0.012 and p < 0.0001, respectively). No significant difference in expression was observed for CXCR7. A high meth-ylation level (>40%) of the CXCL12 promoter was observed in onlya few tumoural samples (5/23) and was associated with a lower expression of the gene (p = 0.03). Stromal cells, rather than the tumour itself, are mainly responsible for the expression of both CXCL12 and CXCR4 expression in HNSCC. CXCR7 expression did not differ between the two compartments and was not related to CXCL12 or CXCR4 expression. Finally, the methylation of the CXCL12 promoter could only explain the low intra-tumoural expression of this gene in 20% of cases.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>25474514</pmid><doi>10.1097/PAT.0000000000000191</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-7074-9282</orcidid></addata></record> |
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| ispartof | Pathology, 2015-01, Vol.47 (1), p.45-50 |
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| subjects | Adult Aged Biochemistry, Molecular Biology Biomarkers, Tumor - analysis Cancer Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Chemokine CXCL12 - analysis Chemokine CXCL12 - biosynthesis Chemokine CXCL12 - genetics CXCL12 CXCR4 CXCR7 DNA Methylation Female head and neck cancer Head and Neck Neoplasms - genetics Head and Neck Neoplasms - metabolism Head and Neck Neoplasms - pathology Humans Immunohistochemistry laser microdissection Life Sciences Male Microdissection Middle Aged Neoplasm Invasiveness oral cancer Promoter Regions, Genetic Receptors, CXCR - analysis Receptors, CXCR - biosynthesis Receptors, CXCR4 - analysis Receptors, CXCR4 - biosynthesis Reverse Transcriptase Polymerase Chain Reaction SDF-1 Squamous Cell Carcinoma of Head and Neck stroma Tumor Microenvironment - physiology |
| title | CXCL12 and CXCR4, but not CXCR7, are primarily expressed by the stroma in head and neck squamous cell carcinoma |
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