The Laminin-α1 Chain-Derived Peptide, AG73, Binds to Syndecans on MDA-231 Breast Cancer Cells and Alters Filopodium Formation
Breast cancer is one of the most common forms of cancer affecting women in the United States, second only to skin cancers. Although treatments have been developed to combat primary breast cancer, metastasis remains a leading cause of death. An early step of metastasis is cancer cell invasion through...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2019/9192516 |
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| author | Madhavi Puchalapalli Liang Mu Chevaunne Edwards Benjamin Kaplan-Singer Pearl Eni Kiran Belani David Finkelstein Arpan Patel Megan Sayyad Jennifer E. Koblinski |
| author_facet | Madhavi Puchalapalli Liang Mu Chevaunne Edwards Benjamin Kaplan-Singer Pearl Eni Kiran Belani David Finkelstein Arpan Patel Megan Sayyad Jennifer E. Koblinski |
| author_sort | Madhavi Puchalapalli |
| collection | DOAJ |
| description | Breast cancer is one of the most common forms of cancer affecting women in the United States, second only to skin cancers. Although treatments have been developed to combat primary breast cancer, metastasis remains a leading cause of death. An early step of metastasis is cancer cell invasion through the basement membrane. However, this process is not yet well understood. AG73, a synthetic laminin-α1 chain peptide, plays an important role in cell adhesion and has previously been linked to migration, invasion, and metastasis. Thus, we aimed to identify the binding partner of AG73 on breast cancer cells that could mediate cancer progression. We performed adhesion assays using MCF10A, T47D, SUM1315, and MDA-231 breast cell lines and found that AG73 binds to syndecans (Sdcs) 1, 2, and 4. This interaction was inhibited when we silenced Sdcs 1 and/or 4 in MDA-231 cells, indicating the importance of these receptors in this relationship. Through actin staining, we found that silencing of Sdc 1, 2, and 4 expression in MDA-231 cells exhibits a decrease in the length and number of filopodia bound to AG73. Expression of mouse Sdcs 1, 2, and 4 in MDA-231 cells provides rescue in filopodia, and overexpression of Sdcs 1 and 2 leads to increased filopodium length and number. Our findings demonstrate an intrinsic interaction between AG73 in the tumor environment and the Sdcs on breast cancer cells in supporting tumor cell adhesion and invasion through filopodia, an important step in cancer metastasis. |
| format | Article |
| id | doaj-art-1024d60fa3404aa4bc27dbc495854190 |
| institution | Kabale University |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-1024d60fa3404aa4bc27dbc4958541902025-08-20T03:55:44ZengWileyAnalytical Cellular Pathology2210-71772210-71852019-01-01201910.1155/2019/91925169192516The Laminin-α1 Chain-Derived Peptide, AG73, Binds to Syndecans on MDA-231 Breast Cancer Cells and Alters Filopodium FormationMadhavi Puchalapalli0Liang Mu1Chevaunne Edwards2Benjamin Kaplan-Singer3Pearl Eni4Kiran Belani5David Finkelstein6Arpan Patel7Megan Sayyad8Jennifer E. Koblinski9Department of Pathology, Virginia Commonwealth University, School of Medicine, Massey Cancer Institute, Richmond, VA, USADepartment of Pathology, Women’s Cancer Research Program, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Institute, Northwestern University, Chicago, IL, USADepartment of Pathology, Virginia Commonwealth University, School of Medicine, Massey Cancer Institute, Richmond, VA, USACraniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USADepartment of Pathology, Women’s Cancer Research Program, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Institute, Northwestern University, Chicago, IL, USACraniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USADepartment of Pathology, Women’s Cancer Research Program, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Institute, Northwestern University, Chicago, IL, USADepartment of Pathology, Women’s Cancer Research Program, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Institute, Northwestern University, Chicago, IL, USADepartment of Pathology, Virginia Commonwealth University, School of Medicine, Massey Cancer Institute, Richmond, VA, USADepartment of Pathology, Virginia Commonwealth University, School of Medicine, Massey Cancer Institute, Richmond, VA, USABreast cancer is one of the most common forms of cancer affecting women in the United States, second only to skin cancers. Although treatments have been developed to combat primary breast cancer, metastasis remains a leading cause of death. An early step of metastasis is cancer cell invasion through the basement membrane. However, this process is not yet well understood. AG73, a synthetic laminin-α1 chain peptide, plays an important role in cell adhesion and has previously been linked to migration, invasion, and metastasis. Thus, we aimed to identify the binding partner of AG73 on breast cancer cells that could mediate cancer progression. We performed adhesion assays using MCF10A, T47D, SUM1315, and MDA-231 breast cell lines and found that AG73 binds to syndecans (Sdcs) 1, 2, and 4. This interaction was inhibited when we silenced Sdcs 1 and/or 4 in MDA-231 cells, indicating the importance of these receptors in this relationship. Through actin staining, we found that silencing of Sdc 1, 2, and 4 expression in MDA-231 cells exhibits a decrease in the length and number of filopodia bound to AG73. Expression of mouse Sdcs 1, 2, and 4 in MDA-231 cells provides rescue in filopodia, and overexpression of Sdcs 1 and 2 leads to increased filopodium length and number. Our findings demonstrate an intrinsic interaction between AG73 in the tumor environment and the Sdcs on breast cancer cells in supporting tumor cell adhesion and invasion through filopodia, an important step in cancer metastasis.http://dx.doi.org/10.1155/2019/9192516 |
| spellingShingle | Madhavi Puchalapalli Liang Mu Chevaunne Edwards Benjamin Kaplan-Singer Pearl Eni Kiran Belani David Finkelstein Arpan Patel Megan Sayyad Jennifer E. Koblinski The Laminin-α1 Chain-Derived Peptide, AG73, Binds to Syndecans on MDA-231 Breast Cancer Cells and Alters Filopodium Formation Analytical Cellular Pathology |
| title | The Laminin-α1 Chain-Derived Peptide, AG73, Binds to Syndecans on MDA-231 Breast Cancer Cells and Alters Filopodium Formation |
| title_full | The Laminin-α1 Chain-Derived Peptide, AG73, Binds to Syndecans on MDA-231 Breast Cancer Cells and Alters Filopodium Formation |
| title_fullStr | The Laminin-α1 Chain-Derived Peptide, AG73, Binds to Syndecans on MDA-231 Breast Cancer Cells and Alters Filopodium Formation |
| title_full_unstemmed | The Laminin-α1 Chain-Derived Peptide, AG73, Binds to Syndecans on MDA-231 Breast Cancer Cells and Alters Filopodium Formation |
| title_short | The Laminin-α1 Chain-Derived Peptide, AG73, Binds to Syndecans on MDA-231 Breast Cancer Cells and Alters Filopodium Formation |
| title_sort | laminin α1 chain derived peptide ag73 binds to syndecans on mda 231 breast cancer cells and alters filopodium formation |
| url | http://dx.doi.org/10.1155/2019/9192516 |
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