Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer
Early detection and discovery of new therapeutic targets are urgently needed to improve the breast cancer treatment outcome. Here we conducted an official clinical trial with cross-validation to corroborate human plasma Hsp90α as a novel breast cancer biomarker. Importantly, similar results were not...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/14/7747 |
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| author | Qiaoyun Hou Shuohua Chen Qi An Boya Li Yan Fu Yongzhang Luo |
| author_facet | Qiaoyun Hou Shuohua Chen Qi An Boya Li Yan Fu Yongzhang Luo |
| author_sort | Qiaoyun Hou |
| collection | DOAJ |
| description | Early detection and discovery of new therapeutic targets are urgently needed to improve the breast cancer treatment outcome. Here we conducted an official clinical trial with cross-validation to corroborate human plasma Hsp90α as a novel breast cancer biomarker. Importantly, similar results were noticed in detecting early-stage breast cancer patients. Additionally, levels of plasma Hsp90α in breast cancer patients were gradually elevated as their clinical stages of regional lymph nodes advanced. In orthotopic breast cancer mouse models, administrating with recombinant Hsp90α protein increased both the primary tumor lymphatic vessel density and sentinel lymph node metastasis by 2 and 10 times, respectively. What is more, Hsp90α neutralizing antibody treatment approximately reduced 70% of lymphatic vessel density and 90% of sentinel lymph node metastasis. In the in vitro study, we demonstrated the role of extracellular Hsp90α (eHsp90α) as a pro-lymphangiogenic factor, which significantly enhanced migration and tube formation abilities of lymphatic endothelial cells (LECs). Mechanistically, eHsp90α signaled to the AKT pathway through low-density lipoprotein receptor-related protein 1 (LRP1) to upregulate the expression and secretion of CXCL8 in the lymphangiogenic process. Collectively, this study proves that plasma Hsp90α serves as an auxiliary diagnosis biomarker and eHsp90α as a molecular mediator promoting lymphangiogenesis in breast cancer. |
| first_indexed | 2024-03-10T09:36:14Z |
| format | Article |
| id | doaj.art-5b70889ca0e44dc1acb7dd8cc6ca0ea5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:36:14Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5b70889ca0e44dc1acb7dd8cc6ca0ea52023-11-22T04:03:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214774710.3390/ijms22147747Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast CancerQiaoyun Hou0Shuohua Chen1Qi An2Boya Li3Yan Fu4Yongzhang Luo5Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaCancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaCancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaCancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaCancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaCancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaEarly detection and discovery of new therapeutic targets are urgently needed to improve the breast cancer treatment outcome. Here we conducted an official clinical trial with cross-validation to corroborate human plasma Hsp90α as a novel breast cancer biomarker. Importantly, similar results were noticed in detecting early-stage breast cancer patients. Additionally, levels of plasma Hsp90α in breast cancer patients were gradually elevated as their clinical stages of regional lymph nodes advanced. In orthotopic breast cancer mouse models, administrating with recombinant Hsp90α protein increased both the primary tumor lymphatic vessel density and sentinel lymph node metastasis by 2 and 10 times, respectively. What is more, Hsp90α neutralizing antibody treatment approximately reduced 70% of lymphatic vessel density and 90% of sentinel lymph node metastasis. In the in vitro study, we demonstrated the role of extracellular Hsp90α (eHsp90α) as a pro-lymphangiogenic factor, which significantly enhanced migration and tube formation abilities of lymphatic endothelial cells (LECs). Mechanistically, eHsp90α signaled to the AKT pathway through low-density lipoprotein receptor-related protein 1 (LRP1) to upregulate the expression and secretion of CXCL8 in the lymphangiogenic process. Collectively, this study proves that plasma Hsp90α serves as an auxiliary diagnosis biomarker and eHsp90α as a molecular mediator promoting lymphangiogenesis in breast cancer.https://www.mdpi.com/1422-0067/22/14/7747plasma Hsp90αtumor biomarkerbreast cancerlymph node metastasisextracellular Hsp90αlymphangiogenesis |
| spellingShingle | Qiaoyun Hou Shuohua Chen Qi An Boya Li Yan Fu Yongzhang Luo Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer International Journal of Molecular Sciences plasma Hsp90α tumor biomarker breast cancer lymph node metastasis extracellular Hsp90α lymphangiogenesis |
| title | Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer |
| title_full | Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer |
| title_fullStr | Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer |
| title_full_unstemmed | Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer |
| title_short | Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer |
| title_sort | extracellular hsp90α promotes tumor lymphangiogenesis and lymph node metastasis in breast cancer |
| topic | plasma Hsp90α tumor biomarker breast cancer lymph node metastasis extracellular Hsp90α lymphangiogenesis |
| url | https://www.mdpi.com/1422-0067/22/14/7747 |
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