The role of placental growth factor and its blockade in the angiogenesis of Medulloblastoma

• Applicant: Dr. Jonas Klöpper
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 207177782

It was recently discovered by my hosts that placental growth factor (PlGF) is highly expressed in MB-cancer cells and the associated stroma. Moreover, it was found that PlGF blockade could significantly inhibit the MB growth and spinal cord spread in transplanted (orthotopic) as well as in spontaneous Smo/Smo MB models. Based on these preliminary findings, this project aims at unravelling the mechanisms of response to anti-PlGF therapy in MBs using genetically engineered animal models, human cell lines and imaging techniques. This project will be focused on the vasculature of MB and shall be divided into three aims: a) Measure the effect of anti-PIGF-antibody (a-PIGF-AB) on MB vessels: Changes in the MB vascular structure and function in response to PIGF blockade shall be measured using immunohistochemistry and in vivo imaging. The hypothesis is that PIGF blockade with an anti-PIGF-antibody (a-PIGF-AB) will normalise MB tumour vessels. b) Establish if anti-PIGF therapy decreases myeloid bone marrow-derived cell (BMDC) recruitment in MB: The effect of PIGF blockade on the recruitment of subsets of BMDC into spontaneous MBs will be investigated. A decrease in associated-associated macrophages (TAMs) after a-PIGF-AB therapy is anticipated. c) Determine the impact of anti-PIGF therapy on TAM polarisation in MB: TAMs will be isolated at different time points after a-PIGF-AB therapy. Their phenotypes shall be evaluated in vitro using qPCR and multiplex protein arrays. The hypothesis is that a-PIGF-AB therapy will polarise TAMs towards an M1-like (anti-tumour) phenotype and stimulate the anti-tumour immune response.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Rakesh K. Jain, Ph.D.