SFB Researchers to be honored with the DGSS Förderpreis 2016

Deepitha Selvaraj and Vijayan Gangadharan (A03) are the recipients of the DGSS Förderpreis 2016 for pain research in Germany. They were awarded the first place in the basic research category for their work on understanding the role of VEGF signalling in cancer-induced pain. The annual price is awarded for tranlational research and applied basic research that majorly contributet to treating acute and chronic pain. 

Summary of their research:

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Graphical abstract: A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain.

It has been known that ligands of the VEGF family play an important role in tumor angiogenesis. Here, the authors report a novel role for VEGF signaling in cancer pain. They found that the receptors of VEGF were expressed in peripheral sensory nerves and observed that diverse VEGF ligands such as VEGF-A, VEGF-B and PLGF-2 augmented pain sensitivity when administered intraplantar into mice. They demonstrated that the pronociceptive functions of VEGF ligands was mediated by a selective and direct activation of the receptor, VEGFR1, expressed at the peripheral nerve terminals. Using pharmacological approach, the authors observed that VEGF recruited classical tyrosine kinase downstream targets such as Plc-gamma, Src Kinase, PI3K and Erk to cause mechanical and thermal hypersensitivity in mice. VEGF also altered the trafficking of the heat-sensing ion channel, TRPV1, increasing its membrane expression. Furthermore, the authors also found that VEGFR1 was selectively upregulated in the peripheral sensory nerves in human cancer and in mouse models of bone cancer. This selective upregulation of VEGFR1 in sensory nerves correlated with pain scores in patients with pancreatic adenocarcinoma. Similarly, they also observed a significant increase in the expression levels of VEGF ligands such as VEGF-A, VEGF-B and PLGF-2 in the tumor tissue. Local sequestering of VEGF ligands using soluble VEGFR1 (sFlt1) and local blockade of diverse VEGF ligands using neutralizing antibodies attenuated cancer-induced pain. Utilizing a variety of mouse cancer models such as in pancreatic cancer, bone cancer and bone metastases and by using a combination of RNA interference, pharmacology and mouse genetics, this study demonstrated that perturbing expression, activation or signaling of VEGFR1, but not of VEGFR2, in peripheral sensory nerves disrupted cancer-induced pain and tumor-induced remodeling of nerves in mice in vivo.

 

A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain.
Selvaraj D, Gangadharan V, Michalski CW, Kurejova M, Stösser S, Srivastava K, Schweizerhof M, Waltenberger J, Ferrara N, Heppenstall P, Shibuya M, Augustin HG, Kuner R.
Cancer Cell. 2015 Jun 8;27(6):780-96. doi: 10.1016/j.ccell.2015.04.017.
PMID:26058077

 

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