Mapping the genetic basis of breast microcalcifications and their role in metastasis
Abstract Breast cancer screening and early stage diagnosis is typically performed by X-ray mammography, which detects microcalcifications. Despite being one of the most reliable features of nonpalpable breast cancer, the processes by which these microcalcifications form are understudied and largely...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-29330-9 |
| _version_ | 1818994367771181056 |
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| author | Asif Rizwan Santosh Kumar Paidi Chao Zheng Menglin Cheng Ishan Barman Kristine Glunde |
| author_facet | Asif Rizwan Santosh Kumar Paidi Chao Zheng Menglin Cheng Ishan Barman Kristine Glunde |
| author_sort | Asif Rizwan |
| collection | DOAJ |
| description | Abstract Breast cancer screening and early stage diagnosis is typically performed by X-ray mammography, which detects microcalcifications. Despite being one of the most reliable features of nonpalpable breast cancer, the processes by which these microcalcifications form are understudied and largely unknown. In the current work, we have investigated the genetic drivers for the formation of microcalcifications in breast cancer cell lines, and have investigated their involvement in disease progression. We have shown that stable silencing of the Osteopontin (OPN) gene decreased the formation of hydroxyapatite in MDA-MB-231 breast cancer cells in response to osteogenic cocktail. In addition, OPN silencing reduced breast cancer cell migration. Furthermore, breast cancer cells that had spontaneously metastasized to the lungs in a mouse model of breast cancer had largely elevated OPN levels, while circulating tumor cells in the same mouse model contained intermediately increased OPN levels as compared to parental cells. The observed dual roles of the OPN gene reveal the existence of a direct relationship between calcium deposition and the ability of breast cancer cells to metastasize to distant organs, mediated by common genetic factors. |
| first_indexed | 2024-12-20T20:56:50Z |
| format | Article |
| id | doaj.art-97b89b4877bf426ea038050a5b2191c2 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T20:56:50Z |
| publishDate | 2018-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-97b89b4877bf426ea038050a5b2191c22022-12-21T19:26:49ZengNature PortfolioScientific Reports2045-23222018-07-018111010.1038/s41598-018-29330-9Mapping the genetic basis of breast microcalcifications and their role in metastasisAsif Rizwan0Santosh Kumar Paidi1Chao Zheng2Menglin Cheng3Ishan Barman4Kristine Glunde5The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of MedicineDepartment of Mechanical Engineering, Johns Hopkins UniversityDepartment of Mechanical Engineering, Johns Hopkins UniversityThe Johns Hopkins University In Vivo Cellular and Molecular Imaging Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of MedicineDepartment of Mechanical Engineering, Johns Hopkins UniversityThe Johns Hopkins University In Vivo Cellular and Molecular Imaging Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of MedicineAbstract Breast cancer screening and early stage diagnosis is typically performed by X-ray mammography, which detects microcalcifications. Despite being one of the most reliable features of nonpalpable breast cancer, the processes by which these microcalcifications form are understudied and largely unknown. In the current work, we have investigated the genetic drivers for the formation of microcalcifications in breast cancer cell lines, and have investigated their involvement in disease progression. We have shown that stable silencing of the Osteopontin (OPN) gene decreased the formation of hydroxyapatite in MDA-MB-231 breast cancer cells in response to osteogenic cocktail. In addition, OPN silencing reduced breast cancer cell migration. Furthermore, breast cancer cells that had spontaneously metastasized to the lungs in a mouse model of breast cancer had largely elevated OPN levels, while circulating tumor cells in the same mouse model contained intermediately increased OPN levels as compared to parental cells. The observed dual roles of the OPN gene reveal the existence of a direct relationship between calcium deposition and the ability of breast cancer cells to metastasize to distant organs, mediated by common genetic factors.https://doi.org/10.1038/s41598-018-29330-9 |
| spellingShingle | Asif Rizwan Santosh Kumar Paidi Chao Zheng Menglin Cheng Ishan Barman Kristine Glunde Mapping the genetic basis of breast microcalcifications and their role in metastasis Scientific Reports |
| title | Mapping the genetic basis of breast microcalcifications and their role in metastasis |
| title_full | Mapping the genetic basis of breast microcalcifications and their role in metastasis |
| title_fullStr | Mapping the genetic basis of breast microcalcifications and their role in metastasis |
| title_full_unstemmed | Mapping the genetic basis of breast microcalcifications and their role in metastasis |
| title_short | Mapping the genetic basis of breast microcalcifications and their role in metastasis |
| title_sort | mapping the genetic basis of breast microcalcifications and their role in metastasis |
| url | https://doi.org/10.1038/s41598-018-29330-9 |
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