Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent
Abstract The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to ductal epithelial cells in normal breasts of women of African ancestry...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41473-6 |
| _version_ | 1827709471806193664 |
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| author | Brijesh Kumar Aditi S. Khatpe Jiang Guanglong Katie Batic Poornima Bhat-Nakshatri Maggie M. Granatir Rebekah Joann Addison Megan Szymanski Lee Ann Baldridge Constance J. Temm George Sandusky Sandra K. Althouse Michele L. Cote Kathy D. Miller Anna Maria Storniolo Harikrishna Nakshatri |
| author_facet | Brijesh Kumar Aditi S. Khatpe Jiang Guanglong Katie Batic Poornima Bhat-Nakshatri Maggie M. Granatir Rebekah Joann Addison Megan Szymanski Lee Ann Baldridge Constance J. Temm George Sandusky Sandra K. Althouse Michele L. Cote Kathy D. Miller Anna Maria Storniolo Harikrishna Nakshatri |
| author_sort | Brijesh Kumar |
| collection | DOAJ |
| description | Abstract The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to ductal epithelial cells in normal breasts of women of African ancestry compared to those of European ancestry. In this study, we demonstrate that these cells have properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRα and transdifferentiate into adipogenic and osteogenic lineages. PROCR + /ZEB1 + /PDGFRα+ (PZP) cells are enriched in normal breast tissues of women of African compared to European ancestry. PZP: epithelial cell communication results in luminal epithelial cells acquiring basal cell characteristics and IL-6-dependent increase in STAT3 phosphorylation. Furthermore, level of phospho-STAT3 is higher in normal and cancerous breast tissues of women of African ancestry. PZP cells transformed with HRasG12V ± SV40-T/t antigens generate metaplastic carcinoma suggesting that these cells are one of the cells-of-origin of metaplastic breast cancers. |
| first_indexed | 2024-03-10T17:22:30Z |
| format | Article |
| id | doaj.art-75421f2ad75f4636aa0061e39d6146f1 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:22:30Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-75421f2ad75f4636aa0061e39d6146f12023-11-20T10:18:23ZengNature PortfolioNature Communications2041-17232023-09-0114112210.1038/s41467-023-41473-6Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descentBrijesh Kumar0Aditi S. Khatpe1Jiang Guanglong2Katie Batic3Poornima Bhat-Nakshatri4Maggie M. Granatir5Rebekah Joann Addison6Megan Szymanski7Lee Ann Baldridge8Constance J. Temm9George Sandusky10Sandra K. Althouse11Michele L. Cote12Kathy D. Miller13Anna Maria Storniolo14Harikrishna Nakshatri15Department of Surgery, Indiana University School of MedicineDepartment of Surgery, Indiana University School of MedicineDepartment of Medicine, Indiana University School of MedicineDepartment of Surgery, Indiana University School of MedicineDepartment of Surgery, Indiana University School of MedicineDepartment of Pathology and Laboratory Medicine, Indiana University School of MedicineDepartment of Pathology and Laboratory Medicine, Indiana University School of MedicineDepartment of Pathology and Laboratory Medicine, Indiana University School of MedicineDepartment of Pathology and Laboratory Medicine, Indiana University School of MedicineDepartment of Pathology and Laboratory Medicine, Indiana University School of MedicineDepartment of Pathology and Laboratory Medicine, Indiana University School of MedicineDepartment of Biostatistics and Health Data Science, Indiana University School of MedicineRichard M. Fairbanks School of Public Health, Indiana UniversityDepartment of Medicine, Indiana University School of MedicineDepartment of Medicine, Indiana University School of MedicineDepartment of Surgery, Indiana University School of MedicineAbstract The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to ductal epithelial cells in normal breasts of women of African ancestry compared to those of European ancestry. In this study, we demonstrate that these cells have properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRα and transdifferentiate into adipogenic and osteogenic lineages. PROCR + /ZEB1 + /PDGFRα+ (PZP) cells are enriched in normal breast tissues of women of African compared to European ancestry. PZP: epithelial cell communication results in luminal epithelial cells acquiring basal cell characteristics and IL-6-dependent increase in STAT3 phosphorylation. Furthermore, level of phospho-STAT3 is higher in normal and cancerous breast tissues of women of African ancestry. PZP cells transformed with HRasG12V ± SV40-T/t antigens generate metaplastic carcinoma suggesting that these cells are one of the cells-of-origin of metaplastic breast cancers.https://doi.org/10.1038/s41467-023-41473-6 |
| spellingShingle | Brijesh Kumar Aditi S. Khatpe Jiang Guanglong Katie Batic Poornima Bhat-Nakshatri Maggie M. Granatir Rebekah Joann Addison Megan Szymanski Lee Ann Baldridge Constance J. Temm George Sandusky Sandra K. Althouse Michele L. Cote Kathy D. Miller Anna Maria Storniolo Harikrishna Nakshatri Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent Nature Communications |
| title | Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent |
| title_full | Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent |
| title_fullStr | Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent |
| title_full_unstemmed | Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent |
| title_short | Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent |
| title_sort | stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of african descent |
| url | https://doi.org/10.1038/s41467-023-41473-6 |
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