Midkine enhances the angiogenic potential of malignant peripheral nerve sheath tumors

Malignant peripheral nerve sheath tumors (MPNST) are classified as neuroectodermal tumors and mostly present with a histology grading of WHO III-IV. The overall 5-year-survival rate of MPNST patients ranges around 34–52% despite aggressive multimodal therapy. As for other solid tumors an animal model most closely resembles the human condition of local tumor invasion and metastases formation to evaluate new therapeutical approaches. So far, human MPNST cell lines are not tumorigenic in xenotransplanted murine models. The tissue factor midkine is supposed to play an key role in the progressive tumorigenisis of plexiform neurofibromas to MPNSTs. Various cell lines displayed an increase in angiogenesis and tumorigenicity when overexpressing midkine. Two different MPNST cell lines were stably transfected with midkine to enhance MPNST tumorigenicity. Stable transfection of midkine did not affect proliferation or apoptosis when tested when using serum starvation assay. However, we were able to show in HUVEC proliferation assays that midkine transfected MPNST cell lines have a higher angiogenic potential than their parental cells. In a further step, midkine transfected MPNST cell lines are tested whether transfection increased their tumorigenicity.

This work is supported by a scholarship of „Kind-Philipp-Stiftung”.