VEGFR2-Mediated Vascular Dilation as a Mechanism of VEGF-Induced Anemia and Bone Marrow Cell Mobilization
Molecular mechanisms underlying tumor VEGF-induced host anemia and bone marrow cell (BMC) mobilization remain unknown. Here, we report that tumor VEGF markedly induced sinusoidal vasculature dilation in bone marrow (BM) and BMC mobilization to tumors and peripheral tissues in mouse and human tumor m...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714007712 |
| _version_ | 1818522025619095552 |
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| author | Sharon Lim Yin Zhang Danfang Zhang Fang Chen Kayoko Hosaka Ninghan Feng Takahiro Seki Patrik Andersson Jingrong Li Jingwu Zang Baocun Sun Yihai Cao |
| author_facet | Sharon Lim Yin Zhang Danfang Zhang Fang Chen Kayoko Hosaka Ninghan Feng Takahiro Seki Patrik Andersson Jingrong Li Jingwu Zang Baocun Sun Yihai Cao |
| author_sort | Sharon Lim |
| collection | DOAJ |
| description | Molecular mechanisms underlying tumor VEGF-induced host anemia and bone marrow cell (BMC) mobilization remain unknown. Here, we report that tumor VEGF markedly induced sinusoidal vasculature dilation in bone marrow (BM) and BMC mobilization to tumors and peripheral tissues in mouse and human tumor models. Unexpectedly, anti-VEGFR2, but not anti-VEGFR1, treatment completely blocked VEGF-induced anemia and BMC mobilization. Genetic deletion of Vegfr2 in endothelial cells markedly ablated VEGF-stimulated BMC mobilization. Conversely, deletion of the tyrosine kinase domain from Vegfr1 gene (Vegfr1TK−/−) did not affect VEGF-induced BMC mobilization. Analysis of VEGFR1+/VEGFR2+ populations in peripheral blood and BM showed no significant ratio difference between VEGF- and control tumor-bearing animals. These findings demonstrate that vascular dilation through the VEGFR2 signaling is the mechanism underlying VEGF-induced BM mobilization and anemia. Thus, our data provide mechanistic insights on VEGF-induced BMC mobilization in tumors and have therapeutic implications by targeting VEGFR2 for cancer therapy. |
| first_indexed | 2024-12-11T05:27:54Z |
| format | Article |
| id | doaj.art-8aaa527f695e4282b843061a102f907e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T05:27:54Z |
| publishDate | 2014-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-8aaa527f695e4282b843061a102f907e2022-12-22T01:19:31ZengElsevierCell Reports2211-12472014-10-019256958010.1016/j.celrep.2014.09.003VEGFR2-Mediated Vascular Dilation as a Mechanism of VEGF-Induced Anemia and Bone Marrow Cell MobilizationSharon Lim0Yin Zhang1Danfang Zhang2Fang Chen3Kayoko Hosaka4Ninghan Feng5Takahiro Seki6Patrik Andersson7Jingrong Li8Jingwu Zang9Baocun Sun10Yihai Cao11Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, SwedenSimcere Pharmaceutical R&D, Nanjing, 699-18 Xuan Wu Avenue, Jiangsu 210042, ChinaSimcere Pharmaceutical R&D, Nanjing, 699-18 Xuan Wu Avenue, Jiangsu 210042, ChinaDepartment of Pathology, Tianjin Medical University, 22 Qi Xiang Tai Road, Heping, Tianjin 300070, ChinaDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, SwedenMolecular mechanisms underlying tumor VEGF-induced host anemia and bone marrow cell (BMC) mobilization remain unknown. Here, we report that tumor VEGF markedly induced sinusoidal vasculature dilation in bone marrow (BM) and BMC mobilization to tumors and peripheral tissues in mouse and human tumor models. Unexpectedly, anti-VEGFR2, but not anti-VEGFR1, treatment completely blocked VEGF-induced anemia and BMC mobilization. Genetic deletion of Vegfr2 in endothelial cells markedly ablated VEGF-stimulated BMC mobilization. Conversely, deletion of the tyrosine kinase domain from Vegfr1 gene (Vegfr1TK−/−) did not affect VEGF-induced BMC mobilization. Analysis of VEGFR1+/VEGFR2+ populations in peripheral blood and BM showed no significant ratio difference between VEGF- and control tumor-bearing animals. These findings demonstrate that vascular dilation through the VEGFR2 signaling is the mechanism underlying VEGF-induced BM mobilization and anemia. Thus, our data provide mechanistic insights on VEGF-induced BMC mobilization in tumors and have therapeutic implications by targeting VEGFR2 for cancer therapy.http://www.sciencedirect.com/science/article/pii/S2211124714007712 |
| spellingShingle | Sharon Lim Yin Zhang Danfang Zhang Fang Chen Kayoko Hosaka Ninghan Feng Takahiro Seki Patrik Andersson Jingrong Li Jingwu Zang Baocun Sun Yihai Cao VEGFR2-Mediated Vascular Dilation as a Mechanism of VEGF-Induced Anemia and Bone Marrow Cell Mobilization Cell Reports |
| title | VEGFR2-Mediated Vascular Dilation as a Mechanism of VEGF-Induced Anemia and Bone Marrow Cell Mobilization |
| title_full | VEGFR2-Mediated Vascular Dilation as a Mechanism of VEGF-Induced Anemia and Bone Marrow Cell Mobilization |
| title_fullStr | VEGFR2-Mediated Vascular Dilation as a Mechanism of VEGF-Induced Anemia and Bone Marrow Cell Mobilization |
| title_full_unstemmed | VEGFR2-Mediated Vascular Dilation as a Mechanism of VEGF-Induced Anemia and Bone Marrow Cell Mobilization |
| title_short | VEGFR2-Mediated Vascular Dilation as a Mechanism of VEGF-Induced Anemia and Bone Marrow Cell Mobilization |
| title_sort | vegfr2 mediated vascular dilation as a mechanism of vegf induced anemia and bone marrow cell mobilization |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714007712 |
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