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VEGFR2-Mediated Vas...
VEGFR2-Mediated Vascular Dilation as a Mechanism of VEGF-Induced Anemia and Bone Marrow Cell Mobilization
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- Lim, Sharon (author)
- Karolinska Institute, Sweden
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- Zhang, Yin (author)
- Karolinska Institutet,Karolinska Institute, Sweden
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- Zhang, Danfang (author)
- Karolinska Institute, Sweden; Tianjin Medical University, Peoples R China
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- Chen, Fang (author)
- Karolinska Institute, Sweden; Zhejiang Chinese Medical University, Peoples R China
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- Hosaka, Kayoko (author)
- Karolinska Institutet,Karolinska Institute, Sweden
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- Feng, Ninghan (author)
- Karolinska Institute, Sweden; Second Hospital Wuxi, Peoples R China
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- Seki, Takahiro (author)
- Karolinska Institutet,Karolinska Institute, Sweden
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- Andersson, Patrik (author)
- Karolinska Institutet,Karolinska Institute, Sweden
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- Li, Jingrong (author)
- Simcere Pharmaceut RandD, Peoples R China
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- Zang, Jingwu (author)
- Simcere Pharmaceut RandD, Peoples R China
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- Sun, Baocun (author)
- Tianjin Medical University, Peoples R China
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- Cao, Yihai (author)
- Karolinska Institutet,Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Karolinska Institute, Sweden; University of Leicester, England
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(creator_code:org_t)
- Elsevier (Cell Press): OAJ / Elsevier, 2014
- 2014
- English.
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In: Cell Reports. - : Elsevier (Cell Press): OAJ / Elsevier. - 2211-1247. ; 9:2, s. 569-580
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https://doi.org/10.1...
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Abstract
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- 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 (Vegfr1(TK-/-)) 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lim, Sharon
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Zhang, Yin
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Zhang, Danfang
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Chen, Fang
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Hosaka, Kayoko
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Feng, Ninghan
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Seki, Takahiro
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Andersson, Patri ...
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Li, Jingrong
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Zang, Jingwu
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Sun, Baocun
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Cao, Yihai
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
- Articles in the publication
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Cell Reports
- By the university
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Linköping University
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Karolinska Institutet