Aging-induced semaphorin 7a promotes TGF-β1-mediated cell plasticity and breast tumor metastases
Summary: Breast cancer risk is transiently increased in postpartum women, and this risk is prolonged in women whose first childbirth occurs after age 30. We observe elevated semaphorin 7a (SEMA7A) in tumor tissues from patients with breast cancer aged 31–39 diagnosed <10 years after childbirth. I...
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Elsevier
2025-08-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725008137 |
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| author | Kelsey T. Kines Heather R. Fairchild Alan M. Elder Lauren M. Cozzens Zachary P. Strugar Veronica M. Wessells Alexandria R. Becks Weston W. Porter Virginia F. Borges Traci R. Lyons |
| author_facet | Kelsey T. Kines Heather R. Fairchild Alan M. Elder Lauren M. Cozzens Zachary P. Strugar Veronica M. Wessells Alexandria R. Becks Weston W. Porter Virginia F. Borges Traci R. Lyons |
| author_sort | Kelsey T. Kines |
| collection | DOAJ |
| description | Summary: Breast cancer risk is transiently increased in postpartum women, and this risk is prolonged in women whose first childbirth occurs after age 30. We observe elevated semaphorin 7a (SEMA7A) in tumor tissues from patients with breast cancer aged 31–39 diagnosed <10 years after childbirth. In the aged normal murine mammary gland, transforming growth factor β+ (TGF-β+) cells have increased levels of surface SEAM7A compared to the young. TGF-β1 induces SEMA7A expression in non-transformed mammary epithelial and breast cancer cells via multiple mechanisms. In mouse mammary tumor models, we observe accelerated tumor growth and metastases, increased TGF-β+SEMA7A+ cells, and epithelial-to-mesenchymal plasticity in aged mice. SEMA7A knockout and heterozygous littermates reveal that these phenotypes depend on SEMA7A in the host. We further show SEMA7A’s pro-metastatic phenotype and abrogate it via a function-blocking antibody. Collectively, these results highlight the impact aging has on the mammary gland and the risk for breast cancer tumorigenesis. |
| format | Article |
| id | doaj-art-2c5f63ad358b4e3aa0cf0a4af6b037cf |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
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| series | Cell Reports |
| spelling | doaj-art-2c5f63ad358b4e3aa0cf0a4af6b037cf2025-08-20T03:20:04ZengElsevierCell Reports2211-12472025-08-0144811604210.1016/j.celrep.2025.116042Aging-induced semaphorin 7a promotes TGF-β1-mediated cell plasticity and breast tumor metastasesKelsey T. Kines0Heather R. Fairchild1Alan M. Elder2Lauren M. Cozzens3Zachary P. Strugar4Veronica M. Wessells5Alexandria R. Becks6Weston W. Porter7Virginia F. Borges8Traci R. Lyons9Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Cancer Biology Graduate Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADivision of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADivision of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Cancer Biology Graduate Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADivision of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Cancer Biology Graduate Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USAColorado College, Colorado Springs, CO 80946, USADivision of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADivision of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Cancer Biology Graduate Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USADivision of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Young Women’s Breast Cancer Translational Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; University of Colorado Cancer Center, Aurora, CO 80045, USADivision of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Cancer Biology Graduate Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Young Women’s Breast Cancer Translational Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; University of Colorado Cancer Center, Aurora, CO 80045, USA; Corresponding authorSummary: Breast cancer risk is transiently increased in postpartum women, and this risk is prolonged in women whose first childbirth occurs after age 30. We observe elevated semaphorin 7a (SEMA7A) in tumor tissues from patients with breast cancer aged 31–39 diagnosed <10 years after childbirth. In the aged normal murine mammary gland, transforming growth factor β+ (TGF-β+) cells have increased levels of surface SEAM7A compared to the young. TGF-β1 induces SEMA7A expression in non-transformed mammary epithelial and breast cancer cells via multiple mechanisms. In mouse mammary tumor models, we observe accelerated tumor growth and metastases, increased TGF-β+SEMA7A+ cells, and epithelial-to-mesenchymal plasticity in aged mice. SEMA7A knockout and heterozygous littermates reveal that these phenotypes depend on SEMA7A in the host. We further show SEMA7A’s pro-metastatic phenotype and abrogate it via a function-blocking antibody. Collectively, these results highlight the impact aging has on the mammary gland and the risk for breast cancer tumorigenesis.http://www.sciencedirect.com/science/article/pii/S2211124725008137CP: Cancer |
| spellingShingle | Kelsey T. Kines Heather R. Fairchild Alan M. Elder Lauren M. Cozzens Zachary P. Strugar Veronica M. Wessells Alexandria R. Becks Weston W. Porter Virginia F. Borges Traci R. Lyons Aging-induced semaphorin 7a promotes TGF-β1-mediated cell plasticity and breast tumor metastases Cell Reports CP: Cancer |
| title | Aging-induced semaphorin 7a promotes TGF-β1-mediated cell plasticity and breast tumor metastases |
| title_full | Aging-induced semaphorin 7a promotes TGF-β1-mediated cell plasticity and breast tumor metastases |
| title_fullStr | Aging-induced semaphorin 7a promotes TGF-β1-mediated cell plasticity and breast tumor metastases |
| title_full_unstemmed | Aging-induced semaphorin 7a promotes TGF-β1-mediated cell plasticity and breast tumor metastases |
| title_short | Aging-induced semaphorin 7a promotes TGF-β1-mediated cell plasticity and breast tumor metastases |
| title_sort | aging induced semaphorin 7a promotes tgf β1 mediated cell plasticity and breast tumor metastases |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725008137 |
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