Targeting the NG2/CSPG4 proteoglycan retards tumour growth and angiogenesis in preclinical models of GBM and melanoma

Jian Wang, Agnete Svendsen, Justyna Kmiecik, Heike Immervol, Kai Ove Skaftnesmo, Jesús Planagumà, Rolf Kåre Reed, Rolf Bjerkvig, Hrvoje Miletic, Per Øyvind Enger, Cecilie Brekke Rygh, Martha Chekenya*

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    89 Citations (Scopus)

    Abstract

    Aberrant expression of the progenitor marker Neuron-glia 2 (NG2/CSPG4) or melanoma proteoglycan on cancer cells and angiogenic vasculature is associated with an aggressive disease course in several malignancies including glioblastoma multiforme (GBM) and melanoma. Thus, we investigated the mechanism of NG2 mediated malignant progression and its potential as a therapeutic target in clinically relevant GBM and melanoma animal models. Xenografting NG2 overexpressing GBM cell lines resulted in increased growth rate, angiogenesis and vascular permeability compared to control, NG2 negative tumours. The effect of abrogating NG2 function was investigated after intracerebral delivery of lentivirally encoded shRNAs targeting NG2 in patient GBM xenografts as well as in established subcutaneous A375 melanoma tumours. NG2 knockdown reduced melanoma proliferation and increased apoptosis and necrosis. Targeting NG2 in two heterogeneous GBM xenografts significantly reduced tumour growth and oedema levels, angiogenesis and normalised vascular function. Vascular normalisation resulted in increased tumour invasion and decreased apoptosis and necrosis. We conclude that NG2 promotes tumour progression by multiple mechanisms and represents an amenable target for cancer molecular therapy.

    Original languageEnglish
    Article numbere23062
    JournalPLoS ONE
    Volume6
    Issue number7
    DOIs
    Publication statusPublished - 2011

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