Targeting the NG2/CSPG4 Proteoglycan Retards Tumour Growth and Angiogenesis in Preclinical Models of GBM and Melanoma

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

International Business as disciplinary tautology: an ontological perspective

The identity, legitimacy, and sustainability of international business (IB) as a research field are at stake. IB is being overtaken by the evolution of industries and technology, and critical voices challenge its distinctiveness and value. We identify IB’s ambiguous conceptual space, articulate the roots of the problem, and suggest a perspective for re-legitimizing the discipline. Specifically, we contend that redrawing legitimate knowledge boundaries for IB requires an ontological shift. In this respect, we promote a focus on the processual constitution of international entities across time and a reconceptualization of IB as the amalgamation of local and international forces. The perspective we advocate aims to counterbalance the disciplinary tautology suffered by current IB conceptualizations and to open up the discussion on boundary identification in the field