Anti-PTK7 Monoclonal Antibodies Exhibit Anti-Tumor Activity at the Cellular Level and in Mouse Xenograft Models of Esophageal Squamous Cell Carcinoma
PTK7 is a catalytically defective receptor protein tyrosine kinase upregulated in various cancers, including esophageal squamous cell carcinoma (ESCC). In previous studies, we observed a positive correlation between PTK7 expression levels and tumorigenicity in various ESCC cell lines and xenograft m...
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| Veröffentlicht in: | International journal of molecular sciences 2022-10, Vol.23 (20), p.12195 |
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| creator | Kim, Jae Hoon Shin, Won-Sik Lee, Se-Ra Kim, Sanggil Choi, So-Young Lee, Seung-Taek |
| description | PTK7 is a catalytically defective receptor protein tyrosine kinase upregulated in various cancers, including esophageal squamous cell carcinoma (ESCC). In previous studies, we observed a positive correlation between PTK7 expression levels and tumorigenicity in various ESCC cell lines and xenograft mice with ESCC KYSE-30 cells. In this study, we analyzed the effects of anti-PTK7 monoclonal antibodies (mAbs) on the tumorigenic activity in KYSE-30 cells and in mouse xenograft models. PTK7 mAb-32 and mAb-43 bind with a high affinity to the extracellular domain of PTK7. PTK7 mAbs significantly reduced three-dimensional cell proliferation, adhesion, wound healing, and migration. PTK7 mAbs also reduce chemotactic invasiveness by decreasing MMP-9 secretion. PTK7 mAbs decreased actin cytoskeleton levels in the cortical region of KYSE-30 cells. PTK7 mAbs reduced the phosphorylation of ERK, SRC, and FAK. In a mouse xenograft model of ESCC using KYSE-30 cells, PTK7 mAbs reduced tumor growth in terms of volume, weight, and the number of Ki-67-positive cells. These results demonstrated that PTK7 mAbs can inhibit the tumorigenicity of ESCC at the cellular level and in vivo by blocking the function of PTK7. Considering the anticancer activities of PTK7 mAbs, we propose that PTK7 mAbs can be used in an effective treatment strategy for PTK7-positive malignancies, such as ESCC. |
| doi_str_mv | 10.3390/ijms232012195 |
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In previous studies, we observed a positive correlation between PTK7 expression levels and tumorigenicity in various ESCC cell lines and xenograft mice with ESCC KYSE-30 cells. In this study, we analyzed the effects of anti-PTK7 monoclonal antibodies (mAbs) on the tumorigenic activity in KYSE-30 cells and in mouse xenograft models. PTK7 mAb-32 and mAb-43 bind with a high affinity to the extracellular domain of PTK7. PTK7 mAbs significantly reduced three-dimensional cell proliferation, adhesion, wound healing, and migration. PTK7 mAbs also reduce chemotactic invasiveness by decreasing MMP-9 secretion. PTK7 mAbs decreased actin cytoskeleton levels in the cortical region of KYSE-30 cells. PTK7 mAbs reduced the phosphorylation of ERK, SRC, and FAK. In a mouse xenograft model of ESCC using KYSE-30 cells, PTK7 mAbs reduced tumor growth in terms of volume, weight, and the number of Ki-67-positive cells. These results demonstrated that PTK7 mAbs can inhibit the tumorigenicity of ESCC at the cellular level and in vivo by blocking the function of PTK7. Considering the anticancer activities of PTK7 mAbs, we propose that PTK7 mAbs can be used in an effective treatment strategy for PTK7-positive malignancies, such as ESCC.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms232012195</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Actin ; Animal models ; Breast cancer ; Cancer therapies ; Cell culture ; Cell growth ; Cell proliferation ; Chemotherapy ; Cytoskeleton ; Epidermal growth factor ; Esophageal cancer ; Extracellular signal-regulated kinase ; Gelatinase B ; Invasiveness ; Kinases ; Medical prognosis ; Monoclonal antibodies ; Phosphorylation ; Polymerization ; Protein-tyrosine kinase ; Proteins ; Squamous cell carcinoma ; Tumor necrosis factor-TNF ; Tumorigenesis ; Tumorigenicity ; Tumors ; Tyrosine ; Wound healing ; Xenografts ; Xenotransplantation</subject><ispartof>International journal of molecular sciences, 2022-10, Vol.23 (20), p.12195</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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In previous studies, we observed a positive correlation between PTK7 expression levels and tumorigenicity in various ESCC cell lines and xenograft mice with ESCC KYSE-30 cells. In this study, we analyzed the effects of anti-PTK7 monoclonal antibodies (mAbs) on the tumorigenic activity in KYSE-30 cells and in mouse xenograft models. PTK7 mAb-32 and mAb-43 bind with a high affinity to the extracellular domain of PTK7. PTK7 mAbs significantly reduced three-dimensional cell proliferation, adhesion, wound healing, and migration. PTK7 mAbs also reduce chemotactic invasiveness by decreasing MMP-9 secretion. PTK7 mAbs decreased actin cytoskeleton levels in the cortical region of KYSE-30 cells. PTK7 mAbs reduced the phosphorylation of ERK, SRC, and FAK. In a mouse xenograft model of ESCC using KYSE-30 cells, PTK7 mAbs reduced tumor growth in terms of volume, weight, and the number of Ki-67-positive cells. These results demonstrated that PTK7 mAbs can inhibit the tumorigenicity of ESCC at the cellular level and in vivo by blocking the function of PTK7. Considering the anticancer activities of PTK7 mAbs, we propose that PTK7 mAbs can be used in an effective treatment strategy for PTK7-positive malignancies, such as ESCC.</description><subject>Actin</subject><subject>Animal models</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cell proliferation</subject><subject>Chemotherapy</subject><subject>Cytoskeleton</subject><subject>Epidermal growth factor</subject><subject>Esophageal cancer</subject><subject>Extracellular signal-regulated kinase</subject><subject>Gelatinase B</subject><subject>Invasiveness</subject><subject>Kinases</subject><subject>Medical prognosis</subject><subject>Monoclonal antibodies</subject><subject>Phosphorylation</subject><subject>Polymerization</subject><subject>Protein-tyrosine kinase</subject><subject>Proteins</subject><subject>Squamous cell carcinoma</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumorigenesis</subject><subject>Tumorigenicity</subject><subject>Tumors</subject><subject>Tyrosine</subject><subject>Wound healing</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUuP0zAQgCMEEsvCkbslLlwCfjSJfUGqqvIQRSBRJG7WxJm0rhy7azsV-0P4v7jdFWI5eTzz6RuPp6peMvpGCEXf2sOUuOCUcaaaR9UVW3BeU9p2j_-Jn1bPUjpQWsBGXVW_lz7b-tv2c0e-BB-MCx4cOSf7MFhMZP1rb3ubL6l6O08hkqXJ9mTzLYFM8h7JCp2bHUSywRM6An4g1hfdnJD8RB92EcZc7gO6RMJI1ikc97DD0uj7zQxTAS8OsoJorA8TPK-ejOASvrg_r6sf79fb1cd68_XDp9VyUxuheK4FXfRMNM0g204YMRrWjQYaw1F1DNpeib5n7QiCgQTEEaToqRqkkQZB8kFcV-_uvMe5n3Aw6HMEp4_RThBvdQCrH1a83etdOGnVUtHItghe3wtiuJkxZT3ZZMos4LGMpXnHVcOlYKqgr_5DD2GO5bcvlFwo1tEzVd9RJoaUIo5_H8OoPm9ZP9iy-AN0NZ3_</recordid><startdate>20221013</startdate><enddate>20221013</enddate><creator>Kim, Jae Hoon</creator><creator>Shin, Won-Sik</creator><creator>Lee, Se-Ra</creator><creator>Kim, Sanggil</creator><creator>Choi, So-Young</creator><creator>Lee, Seung-Taek</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7300-9784</orcidid><orcidid>https://orcid.org/0000-0001-9432-1320</orcidid></search><sort><creationdate>20221013</creationdate><title>Anti-PTK7 Monoclonal Antibodies Exhibit Anti-Tumor Activity at the Cellular Level and in Mouse Xenograft Models of Esophageal Squamous Cell Carcinoma</title><author>Kim, Jae Hoon ; Shin, Won-Sik ; Lee, Se-Ra ; Kim, Sanggil ; Choi, So-Young ; Lee, Seung-Taek</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-304b1355d8673c3fc17fca5c2e971a6b93bb16fa31a8aeefa83b09d8c8cea82d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Actin</topic><topic>Animal models</topic><topic>Breast cancer</topic><topic>Cancer therapies</topic><topic>Cell culture</topic><topic>Cell growth</topic><topic>Cell proliferation</topic><topic>Chemotherapy</topic><topic>Cytoskeleton</topic><topic>Epidermal growth factor</topic><topic>Esophageal cancer</topic><topic>Extracellular signal-regulated kinase</topic><topic>Gelatinase B</topic><topic>Invasiveness</topic><topic>Kinases</topic><topic>Medical prognosis</topic><topic>Monoclonal antibodies</topic><topic>Phosphorylation</topic><topic>Polymerization</topic><topic>Protein-tyrosine kinase</topic><topic>Proteins</topic><topic>Squamous cell carcinoma</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumorigenesis</topic><topic>Tumorigenicity</topic><topic>Tumors</topic><topic>Tyrosine</topic><topic>Wound healing</topic><topic>Xenografts</topic><topic>Xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Jae Hoon</creatorcontrib><creatorcontrib>Shin, Won-Sik</creatorcontrib><creatorcontrib>Lee, Se-Ra</creatorcontrib><creatorcontrib>Kim, Sanggil</creatorcontrib><creatorcontrib>Choi, So-Young</creatorcontrib><creatorcontrib>Lee, Seung-Taek</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Jae Hoon</au><au>Shin, Won-Sik</au><au>Lee, Se-Ra</au><au>Kim, Sanggil</au><au>Choi, So-Young</au><au>Lee, Seung-Taek</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-PTK7 Monoclonal Antibodies Exhibit Anti-Tumor Activity at the Cellular Level and in Mouse Xenograft Models of Esophageal Squamous Cell Carcinoma</atitle><jtitle>International journal of molecular sciences</jtitle><date>2022-10-13</date><risdate>2022</risdate><volume>23</volume><issue>20</issue><spage>12195</spage><pages>12195-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>PTK7 is a catalytically defective receptor protein tyrosine kinase upregulated in various cancers, including esophageal squamous cell carcinoma (ESCC). In previous studies, we observed a positive correlation between PTK7 expression levels and tumorigenicity in various ESCC cell lines and xenograft mice with ESCC KYSE-30 cells. In this study, we analyzed the effects of anti-PTK7 monoclonal antibodies (mAbs) on the tumorigenic activity in KYSE-30 cells and in mouse xenograft models. PTK7 mAb-32 and mAb-43 bind with a high affinity to the extracellular domain of PTK7. PTK7 mAbs significantly reduced three-dimensional cell proliferation, adhesion, wound healing, and migration. PTK7 mAbs also reduce chemotactic invasiveness by decreasing MMP-9 secretion. PTK7 mAbs decreased actin cytoskeleton levels in the cortical region of KYSE-30 cells. PTK7 mAbs reduced the phosphorylation of ERK, SRC, and FAK. In a mouse xenograft model of ESCC using KYSE-30 cells, PTK7 mAbs reduced tumor growth in terms of volume, weight, and the number of Ki-67-positive cells. These results demonstrated that PTK7 mAbs can inhibit the tumorigenicity of ESCC at the cellular level and in vivo by blocking the function of PTK7. Considering the anticancer activities of PTK7 mAbs, we propose that PTK7 mAbs can be used in an effective treatment strategy for PTK7-positive malignancies, such as ESCC.</abstract><cop>Basel</cop><pub>MDPI AG</pub><doi>10.3390/ijms232012195</doi><orcidid>https://orcid.org/0000-0001-7300-9784</orcidid><orcidid>https://orcid.org/0000-0001-9432-1320</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Actin Animal models Breast cancer Cancer therapies Cell culture Cell growth Cell proliferation Chemotherapy Cytoskeleton Epidermal growth factor Esophageal cancer Extracellular signal-regulated kinase Gelatinase B Invasiveness Kinases Medical prognosis Monoclonal antibodies Phosphorylation Polymerization Protein-tyrosine kinase Proteins Squamous cell carcinoma Tumor necrosis factor-TNF Tumorigenesis Tumorigenicity Tumors Tyrosine Wound healing Xenografts Xenotransplantation |
| title | Anti-PTK7 Monoclonal Antibodies Exhibit Anti-Tumor Activity at the Cellular Level and in Mouse Xenograft Models of Esophageal Squamous Cell Carcinoma |
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