MAGE-A3 is a prognostic biomarker for poor clinical outcome in cutaneous squamous cell carcinoma with perineural invasion via modulation of cell proliferation
Perineural invasion is a pathologic process of neoplastic dissemination along and invading into the nerves. Perineural invasion is associated with aggressive disease and a greater likelihood of poor outcomes. In this study, 3 of 9 patients with cutaneous squamous cell carcinoma and perineural invasi...
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| Veröffentlicht in: | PloS one 2020-11, Vol.15 (11), p.e0241551 |
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| description | Perineural invasion is a pathologic process of neoplastic dissemination along and invading into the nerves. Perineural invasion is associated with aggressive disease and a greater likelihood of poor outcomes. In this study, 3 of 9 patients with cutaneous squamous cell carcinoma and perineural invasion exhibited poor clinical outcomes. Tumors from these patients expressed high levels of MAGE-A3, a cancer testis antigen that may contribute to key processes of tumor development. In addition to perineural invasion, the tumors exhibited poor differentiation and deep invasion and were subsequently classified as Brigham and Women's Hospital tumor stage 3. Cyclin E, A and B mRNA levels were increased in these tumors compared with normal skin tissues (102.93±15.03 vs. 27.15±4.59, 36.83±19.41 vs. 11.59±5.83, 343.77±86.49 vs. 95.65±29.25, respectively; p |
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Perineural invasion is associated with aggressive disease and a greater likelihood of poor outcomes. In this study, 3 of 9 patients with cutaneous squamous cell carcinoma and perineural invasion exhibited poor clinical outcomes. Tumors from these patients expressed high levels of MAGE-A3, a cancer testis antigen that may contribute to key processes of tumor development. In addition to perineural invasion, the tumors exhibited poor differentiation and deep invasion and were subsequently classified as Brigham and Women's Hospital tumor stage 3. Cyclin E, A and B mRNA levels were increased in these tumors compared with normal skin tissues (102.93±15.03 vs. 27.15±4.59, 36.83±19.41 vs. 11.59±5.83, 343.77±86.49 vs. 95.65±29.25, respectively; p<0.05). A431 cutaneous squamous cell carcinoma cells pretreated with MAGE-A3 antibody exhibited a decreased percentage S-phase cells (14.13±2.8% vs. 33.97±1.1%; p<0.05) and reduced closure in scratch assays (43.88±5.49% vs. 61.17±3.97%; p = 0.0058). In a syngeneic animal model of squamous cell carcinoma, immunoblots revealed overexpression of MAGE-A3 and cyclin E, A, and B protein in tumors at 6 weeks. However, knockout of MAGE-A3 expression caused a reduction in tumor growth (mean tumor volume 155.3 mm3 vs. 3.2 mm3) compared with parental cells. These results suggest that MAGE-A3 is a key mediator in cancer progression. Moreover, elevated collagen XI and matrix metalloproteases 3, 10, 11, and 13 mRNA levels were observed in poorly differentiated cutaneous squamous cell carcinoma with perineural invasion compared with normal skin tissue (1132.56±882.7 vs. 107.62±183.62, 1118.15±1109.49 vs. 9.5±5, 2603.87±2385.26 vs. 5.29±3, 957.95±627.14 vs. 400.42±967.66, 1149.13±832.18 vs. 19.41±35.62, respectively; p<0.05). In summary, this study highlights the potential prognostic value of MAGE-A3 in clinical outcomes of cutaneous squamous cell carcinoma patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0241551</identifier><identifier>PMID: 33227008</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal models ; Animals ; Antibodies ; Antibodies - pharmacology ; Antigens ; Antigens, Neoplasm - metabolism ; Biology and Life Sciences ; Biomarkers ; Biomarkers, Tumor - metabolism ; Cancer ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell cycle ; Cell Cycle - drug effects ; Cell differentiation ; Cell growth ; Cell Line, Tumor ; Cell proliferation ; Cell Proliferation - drug effects ; Clinical outcomes ; Collagen ; Collagen - genetics ; Collagen - metabolism ; Cyclin E ; Cyclin-dependent kinases ; Cyclins - metabolism ; Dermatology ; Experiments ; Genetic aspects ; Health aspects ; Humans ; Kinases ; Laboratory animals ; Matrix Metalloproteinases - genetics ; Matrix Metalloproteinases - metabolism ; Medical prognosis ; Medicine and Health Sciences ; Metastasis ; Mice ; mRNA ; Neoplasm Invasiveness ; Neoplasm Proteins - metabolism ; Neoplasm Staging ; Nerves ; Patient outcomes ; Patients ; Peripheral Nerves - pathology ; Prognosis ; Proteins ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Skin ; Skin cancer ; Skin Neoplasms - metabolism ; Skin Neoplasms - pathology ; Squamous cell carcinoma ; Testicular cancer ; Treatment Outcome ; Tumor markers ; Tumors ; Up-Regulation - drug effects</subject><ispartof>PloS one, 2020-11, Vol.15 (11), p.e0241551</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Chen et al 2020 Chen et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-11980ebef7310838e4374b50313203ffe967ec1c61a10b8be7b3042438e1312f3</citedby><cites>FETCH-LOGICAL-c692t-11980ebef7310838e4374b50313203ffe967ec1c61a10b8be7b3042438e1312f3</cites><orcidid>0000-0002-8367-8399</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682861/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682861/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33227008$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Hirohashi, Yoshihiko</contributor><creatorcontrib>Chen, Aaron</creatorcontrib><creatorcontrib>Santana, Alexis L</creatorcontrib><creatorcontrib>Doudican, Nicole</creatorcontrib><creatorcontrib>Roudiani, Nazanin</creatorcontrib><creatorcontrib>Laursen, Kristian</creatorcontrib><creatorcontrib>Therrien, Jean-Philippe</creatorcontrib><creatorcontrib>Lee, James</creatorcontrib><creatorcontrib>Felsen, Diane</creatorcontrib><creatorcontrib>Carucci, John A</creatorcontrib><title>MAGE-A3 is a prognostic biomarker for poor clinical outcome in cutaneous squamous cell carcinoma with perineural invasion via modulation of cell proliferation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Perineural invasion is a pathologic process of neoplastic dissemination along and invading into the nerves. Perineural invasion is associated with aggressive disease and a greater likelihood of poor outcomes. In this study, 3 of 9 patients with cutaneous squamous cell carcinoma and perineural invasion exhibited poor clinical outcomes. Tumors from these patients expressed high levels of MAGE-A3, a cancer testis antigen that may contribute to key processes of tumor development. In addition to perineural invasion, the tumors exhibited poor differentiation and deep invasion and were subsequently classified as Brigham and Women's Hospital tumor stage 3. Cyclin E, A and B mRNA levels were increased in these tumors compared with normal skin tissues (102.93±15.03 vs. 27.15±4.59, 36.83±19.41 vs. 11.59±5.83, 343.77±86.49 vs. 95.65±29.25, respectively; p<0.05). A431 cutaneous squamous cell carcinoma cells pretreated with MAGE-A3 antibody exhibited a decreased percentage S-phase cells (14.13±2.8% vs. 33.97±1.1%; p<0.05) and reduced closure in scratch assays (43.88±5.49% vs. 61.17±3.97%; p = 0.0058). In a syngeneic animal model of squamous cell carcinoma, immunoblots revealed overexpression of MAGE-A3 and cyclin E, A, and B protein in tumors at 6 weeks. However, knockout of MAGE-A3 expression caused a reduction in tumor growth (mean tumor volume 155.3 mm3 vs. 3.2 mm3) compared with parental cells. These results suggest that MAGE-A3 is a key mediator in cancer progression. Moreover, elevated collagen XI and matrix metalloproteases 3, 10, 11, and 13 mRNA levels were observed in poorly differentiated cutaneous squamous cell carcinoma with perineural invasion compared with normal skin tissue (1132.56±882.7 vs. 107.62±183.62, 1118.15±1109.49 vs. 9.5±5, 2603.87±2385.26 vs. 5.29±3, 957.95±627.14 vs. 400.42±967.66, 1149.13±832.18 vs. 19.41±35.62, respectively; p<0.05). In summary, this study highlights the potential prognostic value of MAGE-A3 in clinical outcomes of cutaneous squamous cell carcinoma patients.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies - pharmacology</subject><subject>Antigens</subject><subject>Antigens, Neoplasm - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cancer</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell cycle</subject><subject>Cell Cycle - drug effects</subject><subject>Cell differentiation</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Clinical outcomes</subject><subject>Collagen</subject><subject>Collagen - genetics</subject><subject>Collagen - metabolism</subject><subject>Cyclin E</subject><subject>Cyclin-dependent kinases</subject><subject>Cyclins - metabolism</subject><subject>Dermatology</subject><subject>Experiments</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Matrix Metalloproteinases - genetics</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>Medical prognosis</subject><subject>Medicine and Health Sciences</subject><subject>Metastasis</subject><subject>Mice</subject><subject>mRNA</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Neoplasm Staging</subject><subject>Nerves</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Peripheral Nerves - pathology</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Skin</subject><subject>Skin cancer</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>Squamous cell carcinoma</subject><subject>Testicular cancer</subject><subject>Treatment Outcome</subject><subject>Tumor markers</subject><subject>Tumors</subject><subject>Up-Regulation - drug effects</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QDguDFjPlq2rkRhmVdB1YW_LoNaeZkJmOazCbtqH_G32pmp7tMQUEKbXr6vG9OX3KK4jnBU8Iq8nYT-uiVm26DhymmnJQleVCckhmjE0Exe3i0PimepLTBuGS1EI-LE8YorTCuT4vfH-eXF5M5QzYhhbYxrHxIndWosaFV8TtEZEJE25Bv2llvtXIo9J0OLSDrke475SH0CaWbXrX7hQbnkFZRW58t0A_brdEWovXQxyy2fqeSDR7trEJtWPZOdfvXYA7K3IOzBuJt9WnxyCiX4NnwPCu-vr_4cv5hcnV9uTifX020mNFuQsisxtCAqRjBNauBs4o3JWaE5b83BmaiAk20IIrgpm6gahjmlGeSMEINOyteHny3LiQ5RJsk5YKV9SynlonFgVgGtZHbaHM6v2RQVt4WQlxJFXNwDqRQJQZdUsW15lDWqhYlK5XBJV9y3fDs9W7YrW9aWGrwXU5mZDr-4u1arsJOVqKmtSDZ4NVgEMNND6n7R8sDtVK5K-tNyGa6tUnLueBUYJ7PR6amf6HytYTW6ny4jM31keDNSJCZDn52K9WnJBefP_0_e_1tzL4-YtegXLdOwfX7c5DGID-AOoaUIpj75AiW-9m4S0PuZ0MOs5FlL45TvxfdDQP7A28GC8E</recordid><startdate>20201123</startdate><enddate>20201123</enddate><creator>Chen, Aaron</creator><creator>Santana, Alexis L</creator><creator>Doudican, Nicole</creator><creator>Roudiani, Nazanin</creator><creator>Laursen, Kristian</creator><creator>Therrien, Jean-Philippe</creator><creator>Lee, James</creator><creator>Felsen, Diane</creator><creator>Carucci, John A</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-8367-8399</orcidid></search><sort><creationdate>20201123</creationdate><title>MAGE-A3 is a prognostic biomarker for poor clinical outcome in cutaneous squamous cell carcinoma with perineural invasion via modulation of cell proliferation</title><author>Chen, Aaron ; Santana, Alexis L ; Doudican, Nicole ; Roudiani, Nazanin ; Laursen, Kristian ; Therrien, Jean-Philippe ; Lee, James ; Felsen, Diane ; Carucci, John A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-11980ebef7310838e4374b50313203ffe967ec1c61a10b8be7b3042438e1312f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies - 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genetics</topic><topic>Matrix Metalloproteinases - metabolism</topic><topic>Medical prognosis</topic><topic>Medicine and Health Sciences</topic><topic>Metastasis</topic><topic>Mice</topic><topic>mRNA</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Neoplasm Staging</topic><topic>Nerves</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Peripheral Nerves - pathology</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Skin</topic><topic>Skin cancer</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - pathology</topic><topic>Squamous cell carcinoma</topic><topic>Testicular cancer</topic><topic>Treatment Outcome</topic><topic>Tumor markers</topic><topic>Tumors</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Aaron</creatorcontrib><creatorcontrib>Santana, Alexis L</creatorcontrib><creatorcontrib>Doudican, Nicole</creatorcontrib><creatorcontrib>Roudiani, Nazanin</creatorcontrib><creatorcontrib>Laursen, Kristian</creatorcontrib><creatorcontrib>Therrien, Jean-Philippe</creatorcontrib><creatorcontrib>Lee, James</creatorcontrib><creatorcontrib>Felsen, Diane</creatorcontrib><creatorcontrib>Carucci, John A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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 Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Aaron</au><au>Santana, Alexis L</au><au>Doudican, Nicole</au><au>Roudiani, Nazanin</au><au>Laursen, Kristian</au><au>Therrien, Jean-Philippe</au><au>Lee, James</au><au>Felsen, Diane</au><au>Carucci, John A</au><au>Hirohashi, Yoshihiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MAGE-A3 is a prognostic biomarker for poor clinical outcome in cutaneous squamous cell carcinoma with perineural invasion via modulation of cell proliferation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-11-23</date><risdate>2020</risdate><volume>15</volume><issue>11</issue><spage>e0241551</spage><pages>e0241551-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Perineural invasion is a pathologic process of neoplastic dissemination along and invading into the nerves. Perineural invasion is associated with aggressive disease and a greater likelihood of poor outcomes. In this study, 3 of 9 patients with cutaneous squamous cell carcinoma and perineural invasion exhibited poor clinical outcomes. Tumors from these patients expressed high levels of MAGE-A3, a cancer testis antigen that may contribute to key processes of tumor development. In addition to perineural invasion, the tumors exhibited poor differentiation and deep invasion and were subsequently classified as Brigham and Women's Hospital tumor stage 3. Cyclin E, A and B mRNA levels were increased in these tumors compared with normal skin tissues (102.93±15.03 vs. 27.15±4.59, 36.83±19.41 vs. 11.59±5.83, 343.77±86.49 vs. 95.65±29.25, respectively; p<0.05). A431 cutaneous squamous cell carcinoma cells pretreated with MAGE-A3 antibody exhibited a decreased percentage S-phase cells (14.13±2.8% vs. 33.97±1.1%; p<0.05) and reduced closure in scratch assays (43.88±5.49% vs. 61.17±3.97%; p = 0.0058). In a syngeneic animal model of squamous cell carcinoma, immunoblots revealed overexpression of MAGE-A3 and cyclin E, A, and B protein in tumors at 6 weeks. However, knockout of MAGE-A3 expression caused a reduction in tumor growth (mean tumor volume 155.3 mm3 vs. 3.2 mm3) compared with parental cells. These results suggest that MAGE-A3 is a key mediator in cancer progression. Moreover, elevated collagen XI and matrix metalloproteases 3, 10, 11, and 13 mRNA levels were observed in poorly differentiated cutaneous squamous cell carcinoma with perineural invasion compared with normal skin tissue (1132.56±882.7 vs. 107.62±183.62, 1118.15±1109.49 vs. 9.5±5, 2603.87±2385.26 vs. 5.29±3, 957.95±627.14 vs. 400.42±967.66, 1149.13±832.18 vs. 19.41±35.62, respectively; p<0.05). In summary, this study highlights the potential prognostic value of MAGE-A3 in clinical outcomes of cutaneous squamous cell carcinoma patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33227008</pmid><doi>10.1371/journal.pone.0241551</doi><tpages>e0241551</tpages><orcidid>https://orcid.org/0000-0002-8367-8399</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-11, Vol.15 (11), p.e0241551 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2463589386 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animal models Animals Antibodies Antibodies - pharmacology Antigens Antigens, Neoplasm - metabolism Biology and Life Sciences Biomarkers Biomarkers, Tumor - metabolism Cancer Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Cell cycle Cell Cycle - drug effects Cell differentiation Cell growth Cell Line, Tumor Cell proliferation Cell Proliferation - drug effects Clinical outcomes Collagen Collagen - genetics Collagen - metabolism Cyclin E Cyclin-dependent kinases Cyclins - metabolism Dermatology Experiments Genetic aspects Health aspects Humans Kinases Laboratory animals Matrix Metalloproteinases - genetics Matrix Metalloproteinases - metabolism Medical prognosis Medicine and Health Sciences Metastasis Mice mRNA Neoplasm Invasiveness Neoplasm Proteins - metabolism Neoplasm Staging Nerves Patient outcomes Patients Peripheral Nerves - pathology Prognosis Proteins RNA, Messenger - genetics RNA, Messenger - metabolism Skin Skin cancer Skin Neoplasms - metabolism Skin Neoplasms - pathology Squamous cell carcinoma Testicular cancer Treatment Outcome Tumor markers Tumors Up-Regulation - drug effects |
| title | MAGE-A3 is a prognostic biomarker for poor clinical outcome in cutaneous squamous cell carcinoma with perineural invasion via modulation of cell proliferation |
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