Multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by BMP4
Summary: Cell type transition occurs during normal development and under pathological conditions. In prostate cancer bone metastasis, prostate cancer-secreted BMP4 induces endothelial cell-to-osteoblast (EC-to-OSB) transition. Such tumor-induced stromal reprogramming supports prostate cancer progres...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221003564 |
| _version_ | 1830139289031147520 |
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| author | Guoyu Yu Pengfei Shen Yu-Chen Lee Jing Pan Jian H. Song Tianhong Pan Song-Chang Lin Xin Liang Guocan Wang Theocharis Panaretakis Christopher J. Logothetis Gary E. Gallick Li-Yuan Yu-Lee Sue-Hwa Lin |
| author_facet | Guoyu Yu Pengfei Shen Yu-Chen Lee Jing Pan Jian H. Song Tianhong Pan Song-Chang Lin Xin Liang Guocan Wang Theocharis Panaretakis Christopher J. Logothetis Gary E. Gallick Li-Yuan Yu-Lee Sue-Hwa Lin |
| author_sort | Guoyu Yu |
| collection | DOAJ |
| description | Summary: Cell type transition occurs during normal development and under pathological conditions. In prostate cancer bone metastasis, prostate cancer-secreted BMP4 induces endothelial cell-to-osteoblast (EC-to-OSB) transition. Such tumor-induced stromal reprogramming supports prostate cancer progression. We delineate signaling pathways mediating EC-to-OSB transition using EC lines 2H11 and SVR. We found that BMP4-activated pSmad1-Notch-Hey1 pathway inhibits EC migration and tube formation. BMP4-activated GSK3β-βcatenin-Slug pathway stimulates Osx expression. In addition, pSmad1-regulated Dlx2 converges with the Smad1 and β-catenin pathways to stimulate osteocalcin expression. By co-expressing Osx, Dlx2, Slug and Hey1, we were able to achieve EC-to-OSB transition, leading to bone matrix mineralization in the absence of BMP4. In human prostate cancer bone metastasis specimens and MDA-PCa-118b and C4-2b-BMP4 osteogenic xenografts, immunohistochemical analysis showed that β-catenin and pSmad1 are detected in activated osteoblasts rimming the tumor-induced bone. Our results elucidated the pathways and key molecules coordinating prostate cancer-induced stromal programming and provide potential targets for therapeutic intervention. |
| first_indexed | 2024-12-17T08:41:40Z |
| format | Article |
| id | doaj.art-f84fcf5201354a65b4de4e3564d5d5e1 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-17T08:41:40Z |
| publishDate | 2021-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-f84fcf5201354a65b4de4e3564d5d5e12022-12-21T21:56:19ZengElsevieriScience2589-00422021-04-01244102388Multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by BMP4Guoyu Yu0Pengfei Shen1Yu-Chen Lee2Jing Pan3Jian H. Song4Tianhong Pan5Song-Chang Lin6Xin Liang7Guocan Wang8Theocharis Panaretakis9Christopher J. Logothetis10Gary E. Gallick11Li-Yuan Yu-Lee12Sue-Hwa Lin13Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Orthopedic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Corresponding authorDepartment of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA; Corresponding authorSummary: Cell type transition occurs during normal development and under pathological conditions. In prostate cancer bone metastasis, prostate cancer-secreted BMP4 induces endothelial cell-to-osteoblast (EC-to-OSB) transition. Such tumor-induced stromal reprogramming supports prostate cancer progression. We delineate signaling pathways mediating EC-to-OSB transition using EC lines 2H11 and SVR. We found that BMP4-activated pSmad1-Notch-Hey1 pathway inhibits EC migration and tube formation. BMP4-activated GSK3β-βcatenin-Slug pathway stimulates Osx expression. In addition, pSmad1-regulated Dlx2 converges with the Smad1 and β-catenin pathways to stimulate osteocalcin expression. By co-expressing Osx, Dlx2, Slug and Hey1, we were able to achieve EC-to-OSB transition, leading to bone matrix mineralization in the absence of BMP4. In human prostate cancer bone metastasis specimens and MDA-PCa-118b and C4-2b-BMP4 osteogenic xenografts, immunohistochemical analysis showed that β-catenin and pSmad1 are detected in activated osteoblasts rimming the tumor-induced bone. Our results elucidated the pathways and key molecules coordinating prostate cancer-induced stromal programming and provide potential targets for therapeutic intervention.http://www.sciencedirect.com/science/article/pii/S2589004221003564Molecular BiologyCell BiologyCancer |
| spellingShingle | Guoyu Yu Pengfei Shen Yu-Chen Lee Jing Pan Jian H. Song Tianhong Pan Song-Chang Lin Xin Liang Guocan Wang Theocharis Panaretakis Christopher J. Logothetis Gary E. Gallick Li-Yuan Yu-Lee Sue-Hwa Lin Multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by BMP4 iScience Molecular Biology Cell Biology Cancer |
| title | Multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by BMP4 |
| title_full | Multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by BMP4 |
| title_fullStr | Multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by BMP4 |
| title_full_unstemmed | Multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by BMP4 |
| title_short | Multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by BMP4 |
| title_sort | multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by bmp4 |
| topic | Molecular Biology Cell Biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221003564 |
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