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Angiogenic factors ...
Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis.
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Nissen, Lars Johan (författare)
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- Cao, Renhai (författare)
- Karolinska Institutet
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- Hedlund, Eva-Maria (författare)
- Karolinska Institutet
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Wang, Zongwei (författare)
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Zhao, Xing (författare)
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- Wetterskog, Daniel, 1978 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Funa, Keiko, 1949 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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Bråkenhielm, Ebba (författare)
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- Cao, Yihai (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2007
- 2007
- Engelska.
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Ingår i: The Journal of clinical investigation. - 0021-9738. ; 117:10, s. 2766-77
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Tumors produce multiple growth factors, but little is known about the interplay between various angiogenic factors in promoting tumor angiogenesis, growth, and metastasis. Here we show that 2 angiogenic factors frequently upregulated in tumors, PDGF-BB and FGF2, synergistically promote tumor angiogenesis and pulmonary metastasis. Simultaneous overexpression of PDGF-BB and FGF2 in murine fibrosarcomas led to the formation of high-density primitive vascular plexuses, which were poorly coated with pericytes and VSMCs. Surprisingly, overexpression of PDGF-BB alone in tumor cells resulted in dissociation of VSMCs from tumor vessels and decreased recruitment of pericytes. In the absence of FGF2, capillary ECs lacked response to PDGF-BB. However, FGF2 triggers PDGFR-alpha and -beta expression at the transcriptional level in ECs, which acquire hyperresponsiveness to PDGF-BB. Similarly, PDGF-BB-treated VSMCs become responsive to FGF2 stimulation via upregulation of FGF receptor 1 (FGFR1) promoter activity. These findings demonstrate that PDGF-BB and FGF2 reciprocally increase their EC and mural cell responses, leading to disorganized neovascularization and metastasis. Our data suggest that intervention of this non-VEGF reciprocal interaction loop for the tumor vasculature could be an important therapeutic target for the treatment of cancer and metastasis.
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Nissen, Lars Joh ...
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Cao, Renhai
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Hedlund, Eva-Mar ...
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Wang, Zongwei
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Zhao, Xing
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Wetterskog, Dani ...
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visa fler...
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Funa, Keiko, 194 ...
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Bråkenhielm, Ebb ...
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Cao, Yihai
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visa färre...
- Artiklar i publikationen
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The Journal of c ...
- Av lärosätet
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Göteborgs universitet
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Karolinska Institutet