Inhibition of Carbonic Anhydrase IX Suppresses Breast Cancer Cell Motility at the Single-Cell Level
Protein Carbonic Anhydrase IX (CA IX), which is expressed in various hypoxic solid tumors in order to maintain proper pH, is also related to cancer cell adhesion, invasion, and metastasis processes. Here, we investigated whether CA IX inhibition by a highly CA IX selective agent benzenesulfonamide V...
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| Veröffentlicht in: | International journal of molecular sciences 2021-10, Vol.22 (21), p.11571, Article 11571 |
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| description | Protein Carbonic Anhydrase IX (CA IX), which is expressed in various hypoxic solid tumors in order to maintain proper pH, is also related to cancer cell adhesion, invasion, and metastasis processes. Here, we investigated whether CA IX inhibition by a highly CA IX selective agent benzenesulfonamide VD11-4-2 triggers changes in individual cell motility. We seeded breast cancer cells on an extracellular matrix-coated glass-bottomed dish and in a microfluidic device with a gradient flow of epidermal growth factor (EGF), tracked individual cell movement, calculated their migration speeds, and/or followed movement direction. Our results showed that the inhibitor VD11-4-2 decreased the speed of CA IX positive breast cancer cells by 20-26% while not affecting non-cancerous cell migration. The inhibitor suppressed the cell migration velocity increment and hindered cells from reaching their maximum speed. VD11-4-2 also reduced CA IX, expressing cell movement towards the growth factor as a chemoattractant. Such a single cell-based migration assay enabled the comprehensive investigation of the cell motility and revealed that VD11-4-2 shows the ability to suppress breast cancer cell migration at a lower concentration than previously tested CA IX inhibitors. |
| doi_str_mv | 10.3390/ijms222111571 |
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Here, we investigated whether CA IX inhibition by a highly CA IX selective agent benzenesulfonamide VD11-4-2 triggers changes in individual cell motility. We seeded breast cancer cells on an extracellular matrix-coated glass-bottomed dish and in a microfluidic device with a gradient flow of epidermal growth factor (EGF), tracked individual cell movement, calculated their migration speeds, and/or followed movement direction. Our results showed that the inhibitor VD11-4-2 decreased the speed of CA IX positive breast cancer cells by 20-26% while not affecting non-cancerous cell migration. The inhibitor suppressed the cell migration velocity increment and hindered cells from reaching their maximum speed. VD11-4-2 also reduced CA IX, expressing cell movement towards the growth factor as a chemoattractant. Such a single cell-based migration assay enabled the comprehensive investigation of the cell motility and revealed that VD11-4-2 shows the ability to suppress breast cancer cell migration at a lower concentration than previously tested CA IX inhibitors.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms222111571</identifier><identifier>PMID: 34769000</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>Antibiotics ; Benzenesulfonamides ; Biochemistry & Molecular Biology ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Breast Neoplasms - mortality ; Carbonic anhydrase ; Carbonic Anhydrase Inhibitors - pharmacology ; carbonic anhydrase IX ; Carbonic Anhydrase IX - biosynthesis ; Cell adhesion ; Cell adhesion & migration ; Cell Line, Tumor ; Cell Movement - drug effects ; Chemistry ; Chemistry, Multidisciplinary ; Epidermal growth factor ; Experiments ; Extracellular matrix ; Female ; Fibroblasts ; Gradient flow ; Growth factors ; Humans ; Hypoxia ; Influence ; Inhibitors ; Life Sciences & Biomedicine ; MCF-7 Cells ; Medical prognosis ; Metastases ; Metastasis ; Microfluidic devices ; microfluidic system ; Motility ; Physical Sciences ; Science & Technology ; single cell migration ; Solid tumors ; sulfonamide ; Sulfonamides - pharmacology ; Velocity</subject><ispartof>International journal of molecular sciences, 2021-10, Vol.22 (21), p.11571, Article 11571</ispartof><rights>2021 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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Here, we investigated whether CA IX inhibition by a highly CA IX selective agent benzenesulfonamide VD11-4-2 triggers changes in individual cell motility. We seeded breast cancer cells on an extracellular matrix-coated glass-bottomed dish and in a microfluidic device with a gradient flow of epidermal growth factor (EGF), tracked individual cell movement, calculated their migration speeds, and/or followed movement direction. Our results showed that the inhibitor VD11-4-2 decreased the speed of CA IX positive breast cancer cells by 20-26% while not affecting non-cancerous cell migration. The inhibitor suppressed the cell migration velocity increment and hindered cells from reaching their maximum speed. VD11-4-2 also reduced CA IX, expressing cell movement towards the growth factor as a chemoattractant. Such a single cell-based migration assay enabled the comprehensive investigation of the cell motility and revealed that VD11-4-2 shows the ability to suppress breast cancer cell migration at a lower concentration than previously tested CA IX inhibitors.</description><subject>Antibiotics</subject><subject>Benzenesulfonamides</subject><subject>Biochemistry & Molecular Biology</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - mortality</subject><subject>Carbonic anhydrase</subject><subject>Carbonic Anhydrase Inhibitors - pharmacology</subject><subject>carbonic anhydrase IX</subject><subject>Carbonic Anhydrase IX - biosynthesis</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Chemistry</subject><subject>Chemistry, Multidisciplinary</subject><subject>Epidermal growth factor</subject><subject>Experiments</subject><subject>Extracellular matrix</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Gradient flow</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Influence</subject><subject>Inhibitors</subject><subject>Life Sciences & Biomedicine</subject><subject>MCF-7 Cells</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Microfluidic devices</subject><subject>microfluidic system</subject><subject>Motility</subject><subject>Physical Sciences</subject><subject>Science & Technology</subject><subject>single cell migration</subject><subject>Solid tumors</subject><subject>sulfonamide</subject><subject>Sulfonamides - 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drug therapy</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - mortality</topic><topic>Carbonic anhydrase</topic><topic>Carbonic Anhydrase Inhibitors - pharmacology</topic><topic>carbonic anhydrase IX</topic><topic>Carbonic Anhydrase IX - biosynthesis</topic><topic>Cell adhesion</topic><topic>Cell adhesion & migration</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Chemistry</topic><topic>Chemistry, Multidisciplinary</topic><topic>Epidermal growth factor</topic><topic>Experiments</topic><topic>Extracellular matrix</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Gradient flow</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Influence</topic><topic>Inhibitors</topic><topic>Life Sciences & Biomedicine</topic><topic>MCF-7 Cells</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Microfluidic devices</topic><topic>microfluidic system</topic><topic>Motility</topic><topic>Physical Sciences</topic><topic>Science & Technology</topic><topic>single cell migration</topic><topic>Solid tumors</topic><topic>sulfonamide</topic><topic>Sulfonamides - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Janoniene, Agne</au><au>Mazutis, Linas</au><au>Matulis, Daumantas</au><au>Petrikaite, Vilma</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Carbonic Anhydrase IX Suppresses Breast Cancer Cell Motility at the Single-Cell Level</atitle><jtitle>International journal of molecular sciences</jtitle><stitle>INT J MOL SCI</stitle><addtitle>Int J Mol Sci</addtitle><date>2021-10-26</date><risdate>2021</risdate><volume>22</volume><issue>21</issue><spage>11571</spage><pages>11571-</pages><artnum>11571</artnum><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Protein Carbonic Anhydrase IX (CA IX), which is expressed in various hypoxic solid tumors in order to maintain proper pH, is also related to cancer cell adhesion, invasion, and metastasis processes. Here, we investigated whether CA IX inhibition by a highly CA IX selective agent benzenesulfonamide VD11-4-2 triggers changes in individual cell motility. We seeded breast cancer cells on an extracellular matrix-coated glass-bottomed dish and in a microfluidic device with a gradient flow of epidermal growth factor (EGF), tracked individual cell movement, calculated their migration speeds, and/or followed movement direction. Our results showed that the inhibitor VD11-4-2 decreased the speed of CA IX positive breast cancer cells by 20-26% while not affecting non-cancerous cell migration. The inhibitor suppressed the cell migration velocity increment and hindered cells from reaching their maximum speed. VD11-4-2 also reduced CA IX, expressing cell movement towards the growth factor as a chemoattractant. Such a single cell-based migration assay enabled the comprehensive investigation of the cell motility and revealed that VD11-4-2 shows the ability to suppress breast cancer cell migration at a lower concentration than previously tested CA IX inhibitors.</abstract><cop>BASEL</cop><pub>Mdpi</pub><pmid>34769000</pmid><doi>10.3390/ijms222111571</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-5552-6427</orcidid><orcidid>https://orcid.org/0000-0002-6178-6276</orcidid><orcidid>https://orcid.org/0000-0002-4106-5535</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Antibiotics Benzenesulfonamides Biochemistry & Molecular Biology Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Breast Neoplasms - mortality Carbonic anhydrase Carbonic Anhydrase Inhibitors - pharmacology carbonic anhydrase IX Carbonic Anhydrase IX - biosynthesis Cell adhesion Cell adhesion & migration Cell Line, Tumor Cell Movement - drug effects Chemistry Chemistry, Multidisciplinary Epidermal growth factor Experiments Extracellular matrix Female Fibroblasts Gradient flow Growth factors Humans Hypoxia Influence Inhibitors Life Sciences & Biomedicine MCF-7 Cells Medical prognosis Metastases Metastasis Microfluidic devices microfluidic system Motility Physical Sciences Science & Technology single cell migration Solid tumors sulfonamide Sulfonamides - pharmacology Velocity |
| title | Inhibition of Carbonic Anhydrase IX Suppresses Breast Cancer Cell Motility at the Single-Cell Level |
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